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Similar Journals
Journal Cover
Antibodies
Journal Prestige (SJR): 0.931
Citation Impact (citeScore): 3
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2073-4468
Published by MDPI Homepage  [84 journals]
  • Antibodies, Vol. 11, Pages 43: The Binding Landscape of Serum Antibodies:
           How Physical and Mathematical Concepts Can Advance Systems Immunology

    • Authors: József Prechl, Krisztián Papp, Ágnes Kovács, Tamás Pfeil
      First page: 43
      Abstract: Antibodies constitute a major component of serum on protein mass basis. We also know that the structural diversity of these antibodies exceeds that of all other proteins in the body and they react with an immense number of molecular targets. What we still cannot quantitatively describe is how antibody abundance is related to affinity, specificity, and cross reactivity. This ignorance has important practical consequences: we also do not have proper biochemical units for characterizing polyclonal serum antibody binding. The solution requires both a theoretical foundation, a physical model of the system, and technology for the experimental confirmation of theory. Here we argue that the quantitative characterization of interactions between serum antibodies and their targets requires systems-level physical chemistry approach and generates results that should help create maps of antibody binding landscape.
      Citation: Antibodies
      PubDate: 2022-06-23
      DOI: 10.3390/antib11030043
      Issue No: Vol. 11, No. 3 (2022)
       
  • Antibodies, Vol. 11, Pages 22: Emerging Role of Antibody-Drug Conjugates
           and Bispecific Antibodies for the Treatment of Multiple Myeloma

    • Authors: Waqqas Tai, Ahsan Wahab, Diana Franco, Zunairah Shah, Aqsa Ashraf, Qurrat-Ul-Ain Abid, Yaqub Nadeem Mohammed, Darshan Lal, Faiz Anwer
      First page: 22
      Abstract: Multiple myeloma (MM) is characterized by malignant proliferation of malignant plasma cells; it is the second most common hematological malignancy associated with significant morbidity. Genetic intricacy, instability, and diverse clinical presentations remain a barrier to cure. The treatment of MM is modernized with the introduction of newer therapeutics agents, i.e., target-specific monoclonal antibodies. The currently available literature lacks the benefits of newer targeted therapy being developed with an aim to reduce side effects and increase effectiveness, compared to conventional chemotherapy regimens. This article aims to review literature about the current available monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies for the treatment of MM.
      Citation: Antibodies
      PubDate: 2022-03-24
      DOI: 10.3390/antib11020022
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 23: Specific Immunoglobulin E and G to Common
           Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center
           Bulgarian Study

    • Authors: Milena Peruhova, Antoaneta Mihova, Iskra Altankova, Tsvetelina Velikova
      First page: 23
      Abstract: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS.
      Citation: Antibodies
      PubDate: 2022-03-29
      DOI: 10.3390/antib11020023
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 24: Effects of Monovalent Salt on
           Protein-Protein Interactions of Dilute and Concentrated Monoclonal
           Antibody Formulations

    • Authors: Amy Y. Xu, Nicholas J. Clark, Joseph Pollastrini, Maribel Espinoza, Hyo-Jin Kim, Sekhar Kanapuram, Bruce Kerwin, Michael J. Treuheit, Susan Krueger, Arnold McAuley, Joseph E. Curtis
      First page: 24
      Abstract: In this study, we used sodium chloride (NaCl) to extensively modulate non-specific protein-protein interactions (PPI) of a humanized anti-streptavidin monoclonal antibody class 2 molecule (ASA-IgG2). The changes in PPI with varying NaCl (CNaCl) and monoclonal antibody (mAb) concentration (CmAb) were assessed using the diffusion interaction parameter kD and second virial coefficient B22 measured from solutions with low to moderate CmAb. The effective structure factor S(q)eff measured from concentrated mAb solutions using small-angle X-ray and neutron scattering (SAXS/SANS) was also used to characterize the PPI. Our results found that the nature of net PPI changed not only with CNaCl, but also with increasing CmAb. As a result, parameters measured from dilute and concentrated mAb samples could lead to different predictions on the stability of mAb formulations. We also compared experimentally determined viscosity results with those predicted from interaction parameters, including kD and S(q)eff. The lack of a clear correlation between interaction parameters and measured viscosity values indicates that the relationship between viscosity and PPI is concentration-dependent. Collectively, the behavior of flexible mAb molecules in concentrated solutions may not be correctly predicted using models where proteins are considered to be uniform colloid particles defined by parameters derived from low CmAb.
      Citation: Antibodies
      PubDate: 2022-03-31
      DOI: 10.3390/antib11020024
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 25: Cellular, Antibody and Cytokine Pathways in
           Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the
           Puzzle'

    • Authors: Snezhina Lazova, Yulia Dimitrova, Diana Hristova, Iren Tzotcheva, Tsvetelina Velikova
      First page: 25
      Abstract: The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first.
      Citation: Antibodies
      PubDate: 2022-04-01
      DOI: 10.3390/antib11020025
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 26: Precision-Cut Tumor Slices (PCTS) as an Ex
           Vivo Model in Immunotherapy Research

    • Authors: Paraskevi Dimou, Sumita Trivedi, Maria Liousia, Reena R. D'Souza, Astero Klampatsa
      First page: 26
      Abstract: Precision-cut tumor slices (PCTS) have recently emerged as important ex vivo human tumor models, offering the opportunity to study individual patient responses to targeted immunotherapies, including CAR-T cell therapies. In this review, an outline of different human tumor models available in laboratory settings is provided, with a focus on the unique characteristics of PCTS. Standard PCTS generation and maintenance procedures are outlined, followed by an in-depth overview of PCTS utilization in preclinical research aiming to better understand the unique functional characteristics of cytotoxic T cells within human tumors. Furthermore, recent studies using PCTS as an ex vivo model for predicting patient responses to immunotherapies and other targeted therapies against solid tumors are thoroughly presented. Finally, the advantages and limitations of the PCTS models are discussed. PCTS are expected to gain momentum and be fully utilized as a significant tool towards better patient stratification and personalized medicine.
      Citation: Antibodies
      PubDate: 2022-04-06
      DOI: 10.3390/antib11020026
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 27: MALDI-TOF-MS-Based Identification of
           Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour

    • Authors: Georg Tscheuschner, Melanie N. Kaiser, Jan Lisec, Denis Beslic, Thilo Muth, Maren Krüger, Hans Werner Mages, Brigitte G. Dorner, Julia Knospe, Jörg A. Schenk, Frank Sellrie, Michael G. Weller
      First page: 27
      Abstract: During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used 35 monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied to the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 60 min and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 °C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0. This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context.
      Citation: Antibodies
      PubDate: 2022-04-14
      DOI: 10.3390/antib11020027
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 28: A Physiologically Based Pharmacokinetic
           Framework for Quantifying Antibody Distribution Gradients from Tumors to
           Tumor-Draining Lymph Nodes

    • Authors: Eric Salgado, Yanguang Cao
      First page: 28
      Abstract: Immune checkpoint blockades prescribed in the neoadjuvant setting are now under active investigation for many types of tumors, and many have shown early success. The primary tumor (PT) and tumor-draining lymph node (TDLN) immune factors, along with adequate therapeutic antibody distributions to the PT and TDLN, are critical for optimal immune activation and anti-tumor efficacy in neoadjuvant immunotherapy. However, it remains largely unknown how much of the antibody can be distributed into the PT-TDLN axis at different clinical scenarios. The goal of the current work is to build a physiologically based pharmacokinetic (PBPK) model framework capable of characterizing antibody distribution gradients in the PT-TDLN axis across various clinical and pathophysiological scenarios. The model was calibrated using clinical data from immuno-PET antibody-imaging studies quantifying antibody pharmacokinetics (PK) in the blood, PTs, and TDLNs. The effects of metastatic lesion location, tumor-induced compression, and inflammation, as well as surgery, on antibody concentration gradients in the PT-TDLN axis were characterized. The PBPK model serves as a valuable tool to predict antibody exposures in various types of tumors, metastases, and the associated lymph node, supporting effective immunotherapy.
      Citation: Antibodies
      PubDate: 2022-04-14
      DOI: 10.3390/antib11020028
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 29: Special Issue “Antibody Engineering
           for Cancer Immunotherapy”

    • Authors: Silvia Crescioli, Ann L. White, Sophia N. Karagiannis
      First page: 29
      Abstract: Since the approval of Rituximab in the late 1990s, the first chimeric monoclonal antibody for the treatment of non-Hodgkin lymphoma, antibody engineering for cancer immunotherapy has become a rapidly growing field, with almost 50 antibody therapeutics approved in the USA and EU and hundreds undergoing testing in clinical trials [...]
      Citation: Antibodies
      PubDate: 2022-04-15
      DOI: 10.3390/antib11020029
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 30: Persistent Hyper IgA as a Marker of Immune
           Deficiency: A Case Report

    • Authors: Russell J. Hopp, Hana B. Niebur
      First page: 30
      Abstract: An elevated IgA level obtained in a 10-year-old male a year after an episode of pneumococcal sepsis led to the discovery of a broad-based IgG-specific antibody deficiency syndrome. The specifics of the case and pertinent literature are presented, including a discussion of the hyper-IgD syndrome. An elevated IgA, greater than two standard deviations above the expected age range should prompt a complete workup for selective antibody deficiency syndrome and adds an additional associated marker of an indolent hyper-IgD syndrome in a different clinical circumstance, although the lack of antibody response to vaccines is atypical of the hyper-IgD syndrome.
      Citation: Antibodies
      PubDate: 2022-04-25
      DOI: 10.3390/antib11020030
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 31: Advances in Chimeric Antigen Receptor (CAR)
           T-Cell Therapies for the Treatment of Primary Brain Tumors

    • Authors: Christopher W. Mount, Luis Nicolas Gonzalez Castro
      First page: 31
      Abstract: Immunotherapy has revolutionized the care of cancer patients. A diverse set of strategies to overcome cancer immunosuppression and enhance the tumor-directed immune response are in clinical use, but have not achieved transformative benefits for brain tumor patients. Adoptive cell therapies, which employ a patient’s own immune cells to generate directed anti-tumor activity, are emerging technologies that hold promise to improve the treatment of primary brain tumors in children and adults. Here, we review recent advances in chimeric antigen receptor (CAR) T-cell therapies for the treatment of aggressive primary brain tumors, including glioblastoma and diffuse midline glioma, H3 K27M-mutant. We highlight current approaches, discuss encouraging investigational data, and describe key challenges in the development and implementation of these types of therapies in the neuro-oncology setting.
      Citation: Antibodies
      PubDate: 2022-04-27
      DOI: 10.3390/antib11020031
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 32: Immune Cell Metabolic Fitness for Life

    • Authors: Kevin S. Bittman
      First page: 32
      Abstract: Adoptive cell therapy holds great promise for treating a myriad of diseases, especially cancer. Within the last decade, immunotherapy has provided a significant leap in the successful treatment of leukemia. The research conducted throughout this period to understand the interrelationships between cancer cells and infiltrating immune cells winds up having one very common feature, bioenergetics. Cancer cells and immune cells both need ATP to perform their individual functions and cancer cells have adopted means to limit immune cell activity via changes in immune cell bioenergetics that redirect immune cell behavior to encourage tumor growth. Current leading strategies for cancer treatment super-charge an individual’s own immune cells against cancer. Successful Chimeric Antigen Receptor T Cells (CAR T) target pathways that ultimately influence bioenergetics. In the last decade, scientists identified that mitochondria play a crucial role in T cell physiology. When modifying T cells to create chimeras, a unique mitochondrial fitness emerges that establishes stemness and persistence. This review highlights many of the key findings leading to this generation’s CAR T treatments and the work currently being done to advance immunotherapy, to empower not just T cells but other immune cells as well against a variety of cancers.
      Citation: Antibodies
      PubDate: 2022-04-30
      DOI: 10.3390/antib11020032
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 33: MPO–ANCA-Positive Granulomatosis with
           Polyangiitis with Rapidly Progressive Glomerulonephritis and Saddle-Nose
           Deformity: A Case Report

    • Authors: Dimitra Petrou, Minas Karagiannis, Petros Nikolopoulos, George Liapis, Sophia Lionaki
      First page: 33
      Abstract: Early diagnosis and initiation of appropriate immunosuppressive treatment remain the cornerstone of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis at the cost of significant toxicity. In this report, we present a case of a 69-year-old female who presented with advanced renal insufficiency and evidence of pulmonary hemorrhage and was MPO–ANCA-positive with a clinical phenotype of granulomatosis with polyangiitis. Organ involvement included rapidly progressive glomerulonephritis (GN), along with extrarenal manifestations (skin, upper and lower respiratory system involvement, and onset of saddle-nose deformity). Kidney biopsy established the diagnosis of pauci-immune crescentic, sclerotic GN. She received therapy with glucocorticoids and cyclophosphamide, mainly due to life-threatening extra-renal manifestations, such as pulmonary hemorrhage. She avoided vasculitis-related death but she developed severe therapy-related toxicity, resulting in the discontinuation of immunosuppressive therapy. Continuous re-evaluation of patients with ANCA-associated vasculitis in terms of response to immunosuppressive therapy and treatment-related toxicity is crucial for their management.
      Citation: Antibodies
      PubDate: 2022-05-09
      DOI: 10.3390/antib11020033
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 34: Mammalian Display Platform for the
           Maturation of Bispecific TCR-Based Molecules

    • Authors: Janine Dilchert, Martin Hofmann, Felix Unverdorben, Roland Kontermann, Sebastian Bunk
      First page: 34
      Abstract: Bispecific T cell receptor (TCR)-based molecules capable of redirecting and activating T cells towards tumor cells represent a novel and promising class of biotherapeutics for the treatment of cancer. Usage of TCRs allows for targeting of intracellularly expressed and highly selective cancer antigens, but also requires a complex maturation process to increase the naturally low affinity and stability of TCRs. Even though TCR domains can be matured via phage and yeast display, these techniques share the disadvantages of non-human glycosylation patterns and the need for a later reformatting into the final bispecific format. Here, we describe the development and application of a Chinese Hamster Ovary (CHO) display for affinity engineering of TCRs in the context of the final bispecific TCR format. The recombinase-mediated cassette exchange (RCME)-based system allows for stable, single-copy integration of bispecific TCR molecules with high efficiency into a defined genetic locus of CHO cells. We used the system to isolate affinity-increased variants of bispecific T cell engaging receptor (TCER) molecules from a library encoding different CDR variants of a model TCR targeting preferentially expressed antigen in melanoma (PRAME). When expressed as a soluble protein, the selected TCER molecules exhibited strong reactivity against PRAME-positive tumor cells associated with a pronounced cytokine release from activated T cells. The obtained data support the usage of the CHO display-based maturation system for TCR affinity maturation in the context of the final bispecific TCER format.
      Citation: Antibodies
      PubDate: 2022-05-10
      DOI: 10.3390/antib11020034
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 35: Long-Term Immunity and Antibody Response:
           Challenges for Developing Efficient COVID-19 Vaccines

    • Authors: Mohammad Reza Sepand, Banafsheh Bigdelou, Jim Q. Ho, Mohammad Sharaf, Alexis J. Lannigan, Ian M. Sullivan, Alecsander P. da Silva, Leland O. Barrett, Scott McGoldrick, Yuvraj Lnu, Shannon E. Lynch, Jared M. Boisclair, Dakarai D. Barnard-Pratt, Steven Zanganeh
      First page: 35
      Abstract: Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of antibody titers have commanded worldwide attention and research. COVID-19 patients have displayed continued severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike-protein-specific antibodies and neutralizing antibodies in longitudinal studies; in addition, cytokine activation has been detected at early steps following SARS-CoV-2 infection. Epitopes that are highly reactive and can mediate long-term antibody responses have been identified at the spike and ORF1ab proteins. The N-terminal domain of the S1 and S2 subunits is the location of important SARS-CoV-2 spike protein epitopes. High sequence identity between earlier and newer variants of SARS-CoV-2 and different degrees of sequence homology among endemic human coronaviruses have been observed. Understanding the extent and duration of protective immunity is consequential for determining the course of the COVID-19 pandemic. Further knowledge of memory responses to different variants of SARS-CoV-2 is needed to improve the design of the vaccine.
      Citation: Antibodies
      PubDate: 2022-05-12
      DOI: 10.3390/antib11020035
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 36: A New Method to Characterize
           Conformation-Specific Antibody by a Combination of Agarose Native Gel
           Electrophoresis and Contact Blotting

    • Authors: Teruo Akuta, Toshiaki Maruyama, Chiaki Sakuma, Masataka Nakagawa, Yui Tomioka, Kevin Entzminger, Jonathan K. Fleming, Ryo Sato, Takashi Shibata, Yasunori Kurosawa, C. J. Okumura, Tsutomu Arakawa
      First page: 36
      Abstract: In this study, we review the agarose native gel electrophoresis that separates proteins and macromolecular complexes in their native state and transfer of the separated proteins from the agarose gel to membranes by contact blotting which retains the native state of these structures. Green fluorescent protein showed functional state both on agarose gel and blotted membrane. Based on the combined procedures, we discovered conformation-specific monoclonal antibodies against PLXDC2 and SARS-CoV-2 spike protein.
      Citation: Antibodies
      PubDate: 2022-05-12
      DOI: 10.3390/antib11020036
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 37: Antibody Light Chains: Key to Increased
           Monoclonal Antibody Yields in Expi293 Cells'

    • Authors: Siqi Gong, Seijal Gautam, Joshua D. Coneglio, Hanna B. Scinto, Ruth M. Ruprecht
      First page: 37
      Abstract: When constructing isogenic recombinant IgM–IgG pairs, we discovered that μ heavy chains strongly prefer partnering with λ light chains for optimal IgM expression in transiently cotransfected Expi293 cells. When μ chains were paired with κ light chains, IgM yields were low but increased by logs—up to 20,000 X—by using λ chains instead. Switching light chains did not alter epitope specificity. For dimeric IgA2, optimal expression involved pairing with λ chains, whereas light-chain preference varied for other immunoglobulin classes. In summary, recombinant IgM production can be drastically increased by using λ chains, an important finding in the use of IgM for mucosal immunoprophylaxis.
      Citation: Antibodies
      PubDate: 2022-05-18
      DOI: 10.3390/antib11020037
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 38: Kinetics of the Neutralizing and Spike
           SARS-CoV-2 Antibodies following the Sinovac Inactivated Virus Vaccine
           Compared to the Pfizer mRNA Vaccine in Singapore

    • Authors: Chin Shern Lau, May Lin Helen Oh, Soon Kieng Phua, Ya Li Liang, Yanfeng Li, Jianxin Huo, Yuhan Huang, Biyan Zhang, Shengli Xu, Tar Choon Aw
      First page: 38
      Abstract: Introduction: We compared the early total spike antibody (S-Ab) and neutralizing antibody (N-Ab) responses to two vaccines. Methods: We studied 96 Pfizer and 34 Sinovac vaccinees over a 14-month period from January 2021 to February 2022. All vaccinees received three doses of one type of vaccine. Antibody levels (Roche Elecsys total S-Ab and the Snibe N-Ab) were tested 10 days after the first dose, 20 days after the second dose, and 20 days after the booster dose. Results: At all time points, the mRNA vaccine generated higher S-Ab and N-Ab responses than the inactivated virus vaccine (S-Ab: first dose 2.48 vs. 0.4 BAU/mL, second dose 2174 vs. 98 BAU/mL, third dose 15,004 vs. 525 BAU/mL; N-Ab: first dose 0.05 vs. 0.02 µg/mL, second dose 3.48 vs. 0.38 µg/mL, third dose 19.8 vs. 0.89 µg/mL). mRNA vaccine recipients had a 6.2/22.2/28.6-fold higher S-Ab and 2.5/9.2/22.2-fold higher N-Ab response than inactivated virus vaccine recipients after the first/second/third inoculations, respectively. Mann–Whitney U analysis confirmed the significant difference in S-Ab and N-Ab titers between vaccination groups at each time point. Conclusions: The mRNA vaccines generated a more robust S-Ab and N-Ab response than the inactivated virus vaccine at all time points after the first, second, and third vaccinations.
      Citation: Antibodies
      PubDate: 2022-05-27
      DOI: 10.3390/antib11020038
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 39: Strategies to Screen Anti-AQP4 Antibodies
           from Yeast Surface Display Libraries

    • Authors: Aric Huang, Wei Jin, Ahmed S. Fahad, Brooklyn K. Mussman, Grazia Paola Nicchia, Bharat Madan, Matheus Oliveira de Souza, J. Daniel Griffin, Jeffrey L. Bennett, Antonio Frigeri, Cory J. Berkland, Brandon J. DeKosky
      First page: 39
      Abstract: A rapid and effective method to identify disease-specific antibodies from clinical patients is important for understanding autoimmune diseases and for the development of effective disease therapies. In neuromyelitis optica (NMO), the identification of antibodies targeting the aquaporin-4 (AQP4) membrane protein traditionally involves the labor-intensive and time-consuming process of single B-cell sorting, followed by antibody cloning, expression, purification, and analysis for anti-AQP4 activity. To accelerate patient-specific antibody discovery, we compared two unique approaches for screening anti-AQP4 antibodies from yeast antibody surface display libraries. Our first approach, cell-based biopanning, has strong advantages for its cell-based display of native membrane-bound AQP4 antigens and is inexpensive and simple to perform. Our second approach, FACS screening using solubilized AQP4 antigens, permits real-time population analysis and precision sorting for specific antibody binding parameters. We found that both cell-based biopanning and FACS screening were effective for the enrichment of AQP4-binding clones. These screening techniques will enable library-scale functional interrogation of large natively paired antibody libraries for comprehensive analysis of anti-AQP4 antibodies in clinical samples and for robust therapeutic discovery campaigns.
      Citation: Antibodies
      PubDate: 2022-06-05
      DOI: 10.3390/antib11020039
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 40: Discovering Novel Small Molecule Compound
           for Prevention of Monoclonal Antibody Self-Association

    • Authors: Lok Hin Lui, Christopher F. van der Walle, Steve Brocchini, Ajoy Velayudhan
      First page: 40
      Abstract: Designing an antibody with the desired affinity to the antigen is challenging, often achieved by lengthening the hydrophobic CDRs, which can lead to aggregation and cause major hindrance to the development of successful biopharmaceutical products. Aggregation can cause immunogenicity, viscosity and stability issues affecting both the safety and quality of the product. As the hydrophobic residues on the CDR are required for direct binding to antigens, it is not always possible to substitute these residues for aggregation-reduction purposes. Therefore, discovery of specific excipients to prevent aggregation is highly desirable for formulation development. Here, we used a combination of in silico screening methods to identify aggregation-prone regions on an aggregation-prone therapeutic antibody. The most aggregation-prone region on the antibody was selected to conduct virtual screening of compounds that can bind to such regions and act as an aggregation breaker. The most promising excipient candidate was further studied alongside plain buffer formulations and formulations with trehalose using coarse-grained molecular dynamics (CGMD) simulations with MARTINI force field. Mean interaction value between two antibody molecules in each formulation was calculated based on 1024 replicates of 512 ns of such CGMD simulations. Corresponding formulations with an excipient:antibody ratio of 1:5 were compared experimentally by measuring the diffusion interaction parameter kD and accelerated stability studies. Although the compound with the highest affinity score did not show any additional protective effects compared with trehalose, this study proved using a combination of in silico tools can aid excipient design and formulation development.
      Citation: Antibodies
      PubDate: 2022-06-08
      DOI: 10.3390/antib11020040
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 41: Development of a Novel Anti-EpCAM
           Monoclonal Antibody for Various Applications

    • Authors: Guanjie Li, Hiroyuki Suzuki, Teizo Asano, Tomohiro Tanaka, Hiroyoshi Suzuki, Mika K. Kaneko, Yukinari Kato
      First page: 41
      Abstract: The epithelial cell adhesion molecule (EpCAM) is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. EpCAM is involved in cell adhesion, proliferation, survival, stemness, and tumorigenesis. Therefore, EpCAM is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-EpCAM monoclonal antibodies (mAbs) using the Cell-Based Immunization and Screening (CBIS) method. We characterized them using flow cytometry, Western blotting, and immunohistochemistry. One of the established recombinant anti-EpCAM mAbs, recEpMab-37 (mouse IgG1, kappa), reacted with EpCAM-overexpressed Chinese hamster ovary-K1 cells (CHO/EpCAM) or a colorectal carcinoma cell line (Caco-2). In contrast, recEpMab-37 did not react with EpCAM-knocked out Caco-2 cells. The KD of recEpMab-37 for CHO/EpCAM and Caco-2 was 2.0 × 10−8 M and 3.2 × 10−8 M, respectively. We observed that EpCAM amino acids between 144 to 164 are involved in recEpMab-37 binding. In Western blot analysis, recEpMab-37 detected the EpCAM of CHO/EpCAM and Caco-2 cells. Furthermore, recEpMab-37 could stain formalin-fixed paraffin-embedded colorectal carcinoma tissues by immunohistochemistry. Taken together, recEpMab-37, established by the CBIS method, is useful for detecting EpCAM in various applications.
      Citation: Antibodies
      PubDate: 2022-06-08
      DOI: 10.3390/antib11020041
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 42: A Simple Method for the Prediction of Human
           Concentration–Time Profiles and Pharmacokinetics of
           Antibody–Drug Conjugates (ADC) from Rats or Monkeys

    • Authors: Iftekhar Mahmood
      First page: 42
      Abstract: Knowledge of human concentration–time profiles from animal data can be useful during early drug development. The objective of this study is to predict human concentration–time profiles of antibody–drug conjugates (ADCs) and subsequently predict pharmacokinetic parameters in humans from rats or monkeys. Eight methods with different exponents of volume of distribution (0.8–1) as well as exponents of clearance (0.85), along with the exponents of volume of distribution for 5 ADCs, were used to predict human concentration–time profiles. The PK parameters were also scaled to humans from monkeys or rats using fixed exponents and compared with the PK parameters predicted from predicted human concentration–time profiles. The results of the study indicated that the exponent 0.9 and the combination of exponents of 0.9 and 0.8 (two exponents, 0.8 and 0.9, were used) were the best method to predict human concentration–time profiles and, subsequently, human PK parameters. The predicted PK parameters from fixed exponents were comparable with the predicted PK parameters estimated from human concentration–time profiles. The proposed methods are applicable to rats or monkeys with the same degree of accuracy. Overall, the proposed methods are robust, accurate, and cost- and time-effective.
      Citation: Antibodies
      PubDate: 2022-06-14
      DOI: 10.3390/antib11020042
      Issue No: Vol. 11, No. 2 (2022)
       
  • Antibodies, Vol. 11, Pages 3: Immune Maturation Effects on Viral
           Neutralization and Avidity of Hyperimmunized Equine Anti-SARS-CoV-2 Sera

    • Authors: Myriam Belén González Viacava, Augusto Varese, Ignacio Mazzitelli, Laura Lanari, Lucía Ávila, María Julia García Vampa, Jorge Geffner, Osvaldo Cascone, José Christian Dokmetjian, Adolfo Rafael de Roodt, Matías Fingermann
      First page: 3
      Abstract: Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries. The experience gained through decades producing polyclonal immunotherapeutics (such as antivenoms) in many of those countries is being redirected to develop similar products able to neutralize SARS-CoV-2 infection. In this study we analyzed the biological activity (viral neutralization or NtAb) and immunochemical properties of hyperimmune horses’ sera (HHS) obtained during initial immunization (I) and posterior re-immunization (R) cycles using the RBD domain of the SARS-CoV-2 spike protein as antigen. HHS at the end of the R cycle showed higher NtAb titers when compared to those after the I cycle (35,585 vs. 7000 mean NtAb, respectively). Moreover, this increase paralleled an increase in avidity (95.2% to 65.2% mean avidity units, respectively). The results presented herein are relevant for manufacturers of these therapeutic tools against COVID-19.
      Citation: Antibodies
      PubDate: 2022-01-02
      DOI: 10.3390/antib11010003
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 4: TCDD Inhibition of IgG1 Production in
           Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro

    • Authors: Ashleigh J. Nicaise, Amye McDonald, Erin Rushing Sears, Trell Sturgis, Barbara L. F. Kaplan
      First page: 4
      Abstract: The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD’s effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD’s EAE disease attenuation.
      Citation: Antibodies
      PubDate: 2022-01-09
      DOI: 10.3390/antib11010004
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 5: New Opportunities in Glycan Engineering for
           Therapeutic Proteins

    • Authors: Xiaotian Zhong, Aaron M. D’Antona, John J. Scarcelli, Jason C. Rouse
      First page: 5
      Abstract: Glycans as sugar polymers are important metabolic, structural, and physiological regulators for cellular and biological functions. They are often classified as critical quality attributes to antibodies and recombinant fusion proteins, given their impacts on the efficacy and safety of biologics drugs. Recent reports on the conjugates of N-acetyl-galactosamine and mannose-6-phosphate for lysosomal degradation, Fab glycans for antibody diversification, as well as sialylation therapeutic modulations and O-linked applications, have been fueling the continued interest in glycoengineering. The current advancements of the human glycome and the development of a comprehensive network in glycosylation pathways have presented new opportunities in designing next-generation therapeutic proteins.
      Citation: Antibodies
      PubDate: 2022-01-10
      DOI: 10.3390/antib11010005
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 6: Engineering an Enhanced EGFR Engager:
           Humanization of Cetuximab for Improved Developability

    • Authors: Dennis R. Goulet, Soumili Chatterjee, Wai-Ping Lee, Andrew B. Waight, Yi Zhu, Amanda Nga-Sze Mak
      First page: 6
      Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose proliferative effects can contribute to the development of many types of solid tumors when overexpressed. For this reason, EGFR inhibitors such as cetuximab can play an important role in treating cancers such as colorectal cancer and head and neck cancer. Cetuximab is a chimeric monoclonal antibody containing mouse variable regions that bind to EGFR and prevent it from signaling. Although cetuximab has been used clinically since 2004 to successfully control solid tumors, advances in protein engineering have created the opportunity to address some of its shortcomings. In particular, the presence of mouse sequences could contribute to immunogenicity in the form of anti-cetuximab antibodies, and an occupied glycosylation site in FR3 can contribute to hypersensitivity reactions and product heterogeneity. Using simple framework graft or sequence-/structure-guided approaches, cetuximab was humanized onto 11 new frameworks. In addition to increasing humanness and removing the VH glycosylation site, dynamic light scattering revealed increases in stability, and bio-layer interferometry confirmed minimal changes in binding affinity, with patterns emerging across the humanization method. This work demonstrates the potential to improve the biophysical and clinical properties of first-generation protein therapeutics and highlights the advantages of computationally guided engineering.
      Citation: Antibodies
      PubDate: 2022-01-13
      DOI: 10.3390/antib11010006
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 7: Antibodies against Platelet Factor 4 and
           Their Associated Pathologies: From HIT/HITT to Spontaneous HIT-Like
           Syndrome, to COVID-19, to VITT/TTS

    • Authors: Emmanuel J. Favaloro, Leonardo Pasalic, Giuseppe Lippi
      First page: 7
      Abstract: Antibodies against platelet factor 4 (PF4), a protein released from alpha-granules of activated platelets, may cause a number of pathophysiological conditions. The most commonly known is heparin-induced thrombocytopenia (HIT), which develops in a small proportion of people treated with the anticoagulant drug heparin. Notably, PF4 binds with high affinity to heparin, and in HIT, complexes of PF4/H may, in a small proportion of susceptible patients, trigger the development of anti-PF4 antibodies and subsequent platelet activation and aggregation, ultimately leading to the development of pathological thrombosis at sites of vessel occlusion. Of more modern interest, antibodies against PF4 may also arise in patients with COVID-19 (Coronavirus Disease 2019) or in patients who have been vaccinated against COVID-19, especially in recipients of adenovirus-based vaccines. For this latter group of patients, the terms VITT (vaccine-induced [immune] thrombotic thrombocytopenia) and TTS (thrombotic thrombocytopenia syndrome) have been coined. Another category associated with this pathophysiology comprises those in whom a precipitating event is not clear; this category is referred to as ‘spontaneous HIT-like syndrome’. Despite its name, it arises as an HIT-mimicking disorder but without antecedent heparin exposure. In this narrative review, we describe the development of antibodies against PF4, and associated pathophysiology, in such conditions.
      Citation: Antibodies
      PubDate: 2022-01-21
      DOI: 10.3390/antib11010007
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 8: Applications of Antibody-Based Antigen
           Delivery Targeted to Dendritic Cells In Vivo

    • Authors: Jessica Bourque, Daniel Hawiger
      First page: 8
      Abstract: Recombinant immunoglobulins, derived from monoclonal antibodies recognizing the defined surface epitopes expressed on dendritic cells, have been employed for the past two decades to deliver antigens to dendritic cells in vivo, serving as critical tools for the investigation of the corresponding T cell responses. These approaches originated with the development of the recombinant chimeric antibody against a multilectin receptor, DEC-205, which is present on subsets of murine and human conventional dendritic cells. Following the widespread application of antigen targeting through DEC-205, similar approaches then utilized other epitopes as entry points for antigens delivered by specific antibodies to multiple types of dendritic cells. Overall, these antigen-delivery methodologies helped to reveal the mechanisms underlying tolerogenic and immunogenic T cell responses orchestrated by dendritic cells. Here, we discuss the relevant experimental strategies as well as their future perspectives, including their translational relevance.
      Citation: Antibodies
      PubDate: 2022-01-25
      DOI: 10.3390/antib11010008
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 9: Acknowledgment to Reviewers of Antibodies in
           2021

    • Authors: Antibodies Editorial Office Antibodies Editorial Office
      First page: 9
      Abstract: Rigorous peer-reviews are the basis of high-quality academic publishing [...]
      Citation: Antibodies
      PubDate: 2022-01-26
      DOI: 10.3390/antib11010009
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 10: Construction of a Humanized Artificial VHH
           Library Reproducing Structural Features of Camelid VHHs for Therapeutics

    • Authors: Taihei Murakami, Shigefumi Kumachi, Yasuhiro Matsunaga, Miwa Sato, Kanako Wakabayashi-Nakao, Hidekazu Masaki, Ryo Yonehara, Maiko Motohashi, Naoto Nemoto, Masayuki Tsuchiya
      First page: 10
      Abstract: A variable domain of heavy chain antibody (VHH) has different binding properties than conventional antibodies. Conventional antibodies prefer binding to the convex portion of the antigen, whereas VHHs prefer epitopes, such as crevices and clefts on the antigen. Therefore, developing candidates with the binding characteristics of camelid VHHs is important. Thus, To this end, a synthetic VHH library that reproduces the structural properties of camelid VHHs was constructed. First, the characteristics of VHHs were classified according to the paratope formation based on crystal structure analyses of the complex structures of VHHs and antigens. Then, we classified 330 complementarity-determining region 3 (CDR3) structures of VHHs from the Protein Data Bank (PDB) into three loop structures: Upright, Half-Roll, and Roll. Moreover, these structures depended on the number of amino acid residues within CDR3. Furthermore, in the Upright loops, several amino acid residues in the FR2 are involved in the paratope formation, along with CDR3, suggesting that the FR2 design in the synthetic library is important. A humanized synthetic VHH library, comprising two sub-libraries, Upright and Roll, was constructed and named PharmaLogical. A validation study confirmed that our PharmaLogical library reproduces VHHs with the characteristics of the paratope formation of the camelid VHHs, and shows good performance in VHH screening.
      Citation: Antibodies
      PubDate: 2022-01-30
      DOI: 10.3390/antib11010010
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 11: Functional Changes of Therapeutic
           Antibodies upon Exposure to Pro-Oxidative Agents

    • Authors: Maxime Lecerf, Robin Lacombe, Alexia Kanyavuz, Jordan D. Dimitrov
      First page: 11
      Abstract: Therapeutic monoclonal antibodies have exerted a transformative impact on clinical practice in last two decades. However, development of a therapeutic antibody remains a complex process. Various physiochemical and functional liabilities can compromise the production or the therapeutic efficacy of antibodies. One of these liabilities is the susceptibility to oxidation. In the present study, we portrayed an oxidation-dependent vulnerability of immunoglobulins that can be of concern for therapeutic antibodies. By using a library of 119 monoclonal IgG1 molecules, containing variable domain matching clinical-stage antibodies, we demonstrated that a substantial number of these molecules acquired antigen-binding polyreactivity upon exposure to ferrous ions. Statistical analyses revealed that the potential for induction of polyreactivity by the redox-active metal ions correlated with a higher number of somatic mutations in V genes encoding variable domains of heavy and light immunoglobulin chains. Moreover, the sensitive antibodies used with biased frequencies particular V gene families encoding variable domains of their light chains. Besides the exposure to ferrous ions the induction of polyreactivity of therapeutic antibodies occurred after contact with an unrelated pro-oxidative substance—hypochlorite ions. Our data also revealed that induction of polyreactivity by pro-oxidative agents did not impact the binding of antibodies to their cognate antigens. The results from this study may contribute for better selection of antibody therapeutics with suitable developability profiles.
      Citation: Antibodies
      PubDate: 2022-02-02
      DOI: 10.3390/antib11010011
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 12: Cryopreservation of Natural Killer Cells
           Pre-Complexed with Innate Cell Engagers

    • Authors: Uwe Reusch, Kristina Ellwanger, Ivica Fucek, Thomas Müller, Ute Schniegler-Mattox, Joachim Koch, Michael Tesar
      First page: 12
      Abstract: Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE® constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE® antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE® construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE® complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE® drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells.
      Citation: Antibodies
      PubDate: 2022-02-09
      DOI: 10.3390/antib11010012
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 13: Anti-SARS-CoV-2 Omicron Antibodies Isolated
           from a SARS-CoV-2 Delta Semi-Immune Phage Display Library

    • Authors: Ivette Mendoza-Salazar, Keyla M. Gómez-Castellano, Edith González-González, Ramsés Gamboa-Suasnavart, Stefany D. Rodríguez-Luna, Giovanni Santiago-Casas, María I. Cortés-Paniagua, Sonia M. Pérez-Tapia, Juan C. Almagro
      First page: 13
      Abstract: This report describes the discovery and characterization of antibodies with potential broad SARS-CoV-2 neutralization profiles. The antibodies were obtained from a phage display library built with the VH repertoire of a convalescent COVID-19 patient who was infected with SARS-CoV-2 B.1.617.2 (Delta). The patient received a single dose of Ad5-nCoV vaccine (Convidecia™, CanSino Biologics Inc.) one month before developing COVID-19 symptoms. Four synthetic VL libraries were used as counterparts of the immune VH repertoire. After three rounds of panning with SARS-CoV-2 receptor-binding domain wildtype (RBD-WT) 34 unique scFvs, were identified, with 27 cross-reactive for the RBD-WT and RBD Delta (RBD-DT), and seven specifics for the RBD-WT. The cross-reactive scFvs were more diverse than the RBD-WT specific ones, being encoded by several IGHV genes from the IGHV1 and IGHV3 families combined with short HCDR3s. Six cross-reactive scFvs and one RBD-WT specific scFv were converted to human IgG1 (hIgG1). Out of the seven antibodies, six blocked the RBD-WT binding to angiotensin converting enzyme 2 (ACE2), suggesting these antibodies may neutralize the SARS-CoV-2 infection. Importantly, one of the antibodies also recognized the RBD from the B.1.1.529 (Omicron) isolate, implying that the VH repertoire of the convalescent patient would protect against SARS-CoV-2 Wildtype, Delta, and Omicron. From a practical viewpoint, the triple cross-reactive antibody provides the substrate for developing therapeutic antibodies with a broad SARS-CoV-2 neutralization profile.
      Citation: Antibodies
      PubDate: 2022-02-10
      DOI: 10.3390/antib11010013
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 14: More Than Meets the Kappa for Antibody
           Superantigen Protein L (PpL)

    • Authors: Wei-Li Ling, Joshua Yi Yeo, Yuen-Ling Ng, Anil Wipat, Samuel Ken-En Gan
      First page: 14
      Abstract: Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, Staphylococcal Protein A (SpA), Streptococcal Protein G (SpG) and Finegoldia Protein L (PpL) are thought to only bind specific regions of human antibodies, allowing for selective purification of antibody isotypes and chains. Clinically, these superantigens are often classified as toxins and increase the virulence of the producing pathogen through unspecific interactions with immune proteins. To perform an in-depth interaction study of these three superantigens with antibodies, bio-layer interferometry (BLI) measurements of their interactions with a permutation panel of 63 IgG1 variants of Pertuzumab and Trastuzumab CDRs grafted to the six human Vκ and seven human VH region families were tested. Through this holistic and systemic analysis of IgG1 variants with various antibody regions modified, comparisons revealed novel PpL–antibody interactions influenced by other non-canonical antibody known light-chain framework regions, whereas SpA and SpG showed relatively consistent interactions. These findings have implications on PpL-based affinity antibody purification and design that can guide the engineering and understanding of PpL-based microbiota-immune effects.
      Citation: Antibodies
      PubDate: 2022-02-11
      DOI: 10.3390/antib11010014
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 15: Diagnostic Performance of PD-L1 versus PD-1
           Expression in Circulating CD20 Cells in Diffuse Large B-Cell Lymphoma

    • Authors: Manal Mohamed Saber
      First page: 15
      Abstract: This study aimed to investigate PD-L1 and PD-1 expression in circulating CD20+ cells in diffuse larger B-cell lymphoma (DLBCL) and to evaluate the predictive and diagnostic performance of PD-L1 versus PD-1 expression in circulating CD20+ cells in DLBCL. Percentages of CD20+, PD-L1+CD20+, and PD-1+CD20+ cells were measured by flow cytometry in 40 DLBCL blood samples and 19 healthy controls. The DLBCL patient group was subdivided into 20 newly diagnosed patients with no treatment yet and 20 patients that had finished six cycles of CHOP therapy. Percentages of PD-L1+CD20+ and PD-1+CD20+ cells were highly significantly increased in pre-therapy patients in comparison to healthy volunteers (p < 0.001). Meanwhile, a significant decrease in percentages of PD-L1+CD20+ and PD-1+CD20+ was observed in post-CHOP therapy patients in comparison to pre-therapy patients (p < 0.001). PD-L1+CD20+ cells were significantly decreased in post-therapy patients when compared to normal controls (p < 0.001), while not for PD-1+CD20+ cells. A strong significant positive correlation between percentages of PD-L1+CD20+ and PD-1+CD20+ was detected in DLBCL patients (p < 0.001). In the pre-therapy group, high PD-L1+CD20+ and PD-1+CD20+ percentages were correlated with serum LDH levels (p = 0.021, p < 0.001). High percentages of PD-1+CD20+ were found in DLBCL patients with splenomegaly (p = 0.027). The results revealed that patients with advanced tumor stages, poor ECOG performance, and non-GCB DLBCL type had increased percentages of PD-L1+CD20+ and PD-1+CD20+ cells. Moreover, PD-L1+CD20+ % and PD-1+CD20+ % were significantly increased in DLBCL patients with bone marrow involvement or B symptoms. The superiority of PD-L1+CD20+ over PD-1+CD20+ was more profound in DLBCL prediction [AUC: 1.0] and in discriminating newly diagnosed patients [AUC: 1.0]. The findings suggest that increased PD-L1/PD-1 expression in peripheral CD20 cells may serve as a companion diagnostic marker for DLBCL. Moreover, percentages of PD-L1+CD20+ cells have better diagnostic performance with higher sensitivity and specificity than PD-1+CD20+ %.
      Citation: Antibodies
      PubDate: 2022-02-16
      DOI: 10.3390/antib11010015
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 16: The Role of Bispecific Antibodies in
           Non-Hodgkin’s Lymphoma: From Structure to Prospective Clinical Use

    • Authors: Rita Tavarozzi, Enrica Manzato
      First page: 16
      Abstract: Bispecific antibodies (bsAbs) are molecules that simultaneously bind two different antigens (Ags). bsAbs represent a very active field in tumor immunotherapy with more than one hundred molecules currently being tested. More specifically, they have elicited a great interest in the setting of non-Hodgkin’s lymphoma (NHLs), where they could represent a viable option for more fragile patients or those resistant to other conventional therapies. This review aims to give a brief overview of the different available bsAb formats and their mechanisms of action, pinpointing the differences between IgG-like and non-IgG-like classes and will then focus on those in advanced clinical development for NHLs.
      Citation: Antibodies
      PubDate: 2022-02-21
      DOI: 10.3390/antib11010016
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 17: Immune- and Non-Immune-Mediated Adverse
           Effects of Monoclonal Antibody Therapy: A Survey of 110 Approved
           Antibodies

    • Authors: Brian A. Baldo
      First page: 17
      Abstract: Identification of new disease-associated biomarkers; specific targeting of such markers by monoclonal antibodies (mAbs); and application of advances in recombinant technology, including the production of humanized and fully human antibodies, has enabled many improved treatment outcomes and successful new biological treatments of some diseases previously neglected or with poor prognoses. Of the 110 mAbs preparations currently approved by the FDA and/or EMA, 46 (including 13 antibody–drug conjugates) recognizing 29 different targets are indicated for the treatment of cancers, and 66, recognizing 48 different targets, are indicated for non-cancer disorders. Despite their specific targeting with the expected accompanying reduced collateral damage for normal healthy non-involved cells, mAbs, may cause types I (anaphylaxis, urticaria), II (e.g., hemolytic anemia, possibly early-onset neutropenia), III (serum sickness, pneumonitis), and IV (Stevens–Johnson syndrome, toxic epidermal necrolysis) hypersensitivities as well as other cutaneous, pulmonary, cardiac, and liver adverse events. MAbs can provoke severe infusion reactions that resemble anaphylaxis and induce a number of systemic, potentially life-threatening syndromes with low frequency. A common feature of most of these syndromes is the release of a cascade of cytokines associated with inflammatory and immunological processes. Epidermal growth factor receptor-targeted antibodies may provoke papulopustular and mucocutaneous eruptions that are not immune-mediated.
      Citation: Antibodies
      PubDate: 2022-02-25
      DOI: 10.3390/antib11010017
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 18: Ramifications of the HLA-I Allelic
           Reactivity of Anti-HLA-E*01:01 and Anti-HLA-E*01:03 Heavy Chain Monoclonal
           Antibodies in Comparison with Anti-HLA-I IgG Reactivity in
           Non-Alloimmunized Males, Melanoma-Vaccine Recipients, and End-Stage Renal
           Disease Patients

    • Authors: Mepur H. Ravindranath, Narendranath M. Ravindranath, Fatiha El Hilali, Senthamil R. Selvan, Edward J. Filippone
      First page: 18
      Abstract: Serum anti-HLA-I IgG are present in non-alloimmunized males, cancer patients, and transplant recipients. Anti-HLA-I antibodies are also present in intravenous immunoglobulin (IVIg), prepared from the plasma of thousands of healthy donors. However, the HLA-Ia reactivity of IVIg diminishes markedly after passing through HLA-E HC-affinity columns, suggesting that the HLA-I reactivity is due to antibodies formed against HLA-E. Hence, we examined whether anti-HLA-E antibodies can react to HLA-I alleles. Monoclonal IgG antibodies (mAbs) against HCs of two HLA-E alleles were generated in Balb/C mice. The antibodies were analyzed using multiplex bead assays on a Luminex platform for HLA-I reactivity. Beads coated with an array of HLA heterodimers admixed with HCs (LABScreen) were used to examine the binding of IgG to different HLA-Ia (31-HLA-A, 50-HLA-B, and 16-HLA-C) and Ib (2-HLA-E, one each of HLA-F and HLA-G) alleles. A striking diversity in the HLA-Ia and/or HLA-Ib reactivity of mAbs was observed. The number of the mAbs reactive to (1) only HLA-E (n = 25); (2) all HLA-Ib isomers (n = 8); (3) HLA-E and HLA-B (n = 5); (4) HLA-E, HLA-B, and HLA-C (n = 30); (5) HLA-E, HLA-A*1101, HLA-B, and HLA-C (n = 83); (6) HLA-E, HLA-A, HLA-B, and HLA-C (n = 54); and (7) HLA-Ib and HLA-Ia (n = 8), in addition to four other minor groups. Monospecificity and polyreactivity were corroborated by HLA-E monospecific and HLA-I shared sequences. The diverse HLA-I reactivity of the mAbs are compared with the pattern of HLA-I reactivity of serum-IgG in non-alloimmunized males, cancer patients, and ESKD patients. The findings unravel the diagnostic potential of the HLA-E monospecific-mAbs and immunomodulatory potentials of IVIg highly mimicking HLA-I polyreactive-mAbs.
      Citation: Antibodies
      PubDate: 2022-03-02
      DOI: 10.3390/antib11010018
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 19: Design and Characterization of Novel
           Antibody-Cytokine Fusion Proteins Based on Interleukin-21

    • Authors: Cesare Di Nitto, Dario Neri, Tobias Weiss, Michael Weller, Roberto De Luca
      First page: 19
      Abstract: Interleukin-21 (IL21) is a pleiotropic cytokine involved in the modulation of both innate and adaptive immunity. IL21 is mainly secreted by natural killer (NK) and activated CD4+ T-cells. The biology of this cytokine can be associated to proinflammatory responses reflecting its potent stimulatory activity of NK and CD8+ T-cells. Here we describe four formats of novel IL21-based antibody–cytokine fusion proteins, targeting the extra domain A (EDA) of fibronectin and explore their potential for cancer treatment. The fusion proteins were designed, expressed, and characterized. F8 in single-chain diabody (scDb) format fused to IL21 at its C-terminus exhibited a promising profile in size exclusion chromatography (SEC) and SDS-PAGE. The lead candidate was further characterized in vitro. A cell-based activity assay on murine cytotoxic T-cells showed that human IL21, compared to murine IL21 partially cross-reacted with the murine receptor. The prototype was able to recognize EDA as demonstrated by immunofluorescence analysis on tumor sections. In an in vivo quantitative biodistribution experiment, F8(scDb)-murine IL21 did not preferentially accumulate at the site of disease after intravenous injection, suggesting that additional protein engineering would be required to improve the tumor-homing properties of IL21-based product.
      Citation: Antibodies
      PubDate: 2022-03-04
      DOI: 10.3390/antib11010019
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 20: Reactivity of Rheumatoid
           Arthritis-Associated Citrulline-Dependent Antibodies to Epstein-Barr Virus
           Nuclear Antigen1-3

    • Authors: Ilaria Fanelli, Paolo Rovero, Paul Robert Hansen, Jette Lautrup Frederiksen, Gunnar Houen, Nicole Hartwig Trier
      First page: 20
      Abstract: Rheumatoid arthritis (RA) is a chronic disease which causes joint inflammation and, ultimately, erosion of the underlying bone. Diagnosis of RA is based on the presence of biomarkers, such as anti-citrullinated protein antibodies (ACPA) and rheumatoid factors, along with clinical symptoms. Much evidence points to a link between the Epstein-Barr virus and RA. In this study, we analyzed ACPA reactivity to citrullinated peptides originating from Epstein-Barr nuclear antigens (EBNA1, EBNA2, and EBNA3) in order to elaborate the diagnostic potential of citrullinated EBNA peptides. Moreover, ACPA cross-reactivity to citrullinated peptides from myelin basic protein (MBP) was analyzed, as citrullinated MBP recently was described to be associated with multiple sclerosis, and some degree of sequence homology between MBP and citrullinated EBNA exists. A peptide from EBNA2, (EBNA2-A, GQGRGRWRG-Cit-GSKGRGRMH) reacted with approximately 70% of all RA sera, whereas only limited reactivity was detected to EBNA1 and EBNA3 peptides. Moreover, screening of ACPA reactivity to hybrid peptides of EBNA3-A (EPDSRDQQS-Cit-GQRRGDENRG) and EBNA2-A and peptides containing citrulline close to the N-terminal confirmed that ACPA sera contain different populations of ACPAs. No notable ACPA reactivity to MBP peptides was found, confirming that ACPAs are specific for RA, and that other factors than the presence of a central Cit-Gly motif are crucial for antibody binding. Collectively, these findings illustrate that citrullinated EBNA2 is an optimal candidate for ACPA detection, supporting current evidence that EBV is linked to RA onset.
      Citation: Antibodies
      PubDate: 2022-03-11
      DOI: 10.3390/antib11010020
      Issue No: Vol. 11, No. 1 (2022)
       
  • Antibodies, Vol. 11, Pages 21: Highly Specific Monoclonal Antibody
           Targeting the Botulinum Neurotoxin Type E Exposed SNAP-25 Neoepitope

    • Authors: Adva Mechaly, Eran Diamant, Ron Alcalay, Alon Ben David, Eyal Dor, Amram Torgeman, Ada Barnea, Meni Girshengorn, Lilach Levin, Eyal Epstein, Ariel Tennenhouse, Sarel J. Fleishman, Ran Zichel, Ohad Mazor
      First page: 21
      Abstract: Botulinum neurotoxin type E (BoNT/E), the fastest acting toxin of all BoNTs, cleaves the 25 kDa synaptosomal-associated protein (SNAP-25) in motor neurons, leading to flaccid paralysis. The specific detection and quantification of the BoNT/E-cleaved SNAP-25 neoepitope can facilitate the development of cell-based assays for the characterization of anti-BoNT/E antibody preparations. In order to isolate highly specific monoclonal antibodies suitable for the in vitro immuno-detection of the exposed neoepitope, mice and rabbits were immunized with an eight amino acid peptide composed of the C-terminus of the cleaved SNAP-25. The immunized rabbits developed a specific and robust polyclonal antibody response, whereas the immunized mice mostly demonstrated a weak antibody response that could not discriminate between the two forms of SNAP-25. An immune scFv phage-display library was constructed from the immunized rabbits and a panel of antibodies was isolated. The sequence alignment of the isolated clones revealed high similarity between both heavy and light chains with exceptionally short HCDR3 sequences. A chimeric scFv-Fc antibody was further expressed and characterized, exhibiting a selective, ultra-high affinity (pM) towards the SNAP-25 neoepitope. Moreover, this antibody enabled the sensitive detection of cleaved SNAP-25 in BoNT/E treated SiMa cells with no cross reactivity with the intact SNAP-25. Thus, by applying an immunization and selection procedure, we have isolated a novel, specific and high-affinity antibody against the BoNT/E-derived SNAP-25 neoepitope. This novel antibody can be applied in in vitro assays that determine the potency of antitoxin preparations and reduce the use of laboratory animals for these purposes.
      Citation: Antibodies
      PubDate: 2022-03-16
      DOI: 10.3390/antib11010021
      Issue No: Vol. 11, No. 1 (2022)
       
 
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