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Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access  
3D Printing in Medicine     Open Access   (Followers: 2)
AADE in Practice     Hybrid Journal   (Followers: 5)
ABCS Health Sciences     Open Access   (Followers: 4)
Abia State University Medical Students' Association Journal     Full-text available via subscription  
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 44)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
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Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Científica Estudiantil     Open Access  
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Acta Scientiarum. Health Sciences     Open Access   (Followers: 1)
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 6)
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Addiction Science & Clinical Practice     Open Access   (Followers: 8)
Addictive Behaviors Reports     Open Access   (Followers: 9)
Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / Health Sciences Journal of Adıyaman University     Open Access  
Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi     Open Access  
Advanced Biomedical Research     Open Access  
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 8)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 6)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26)
Advances in Life Course Research     Hybrid Journal   (Followers: 8)
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Advances in Parkinson's Disease     Open Access  
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Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Regenerative Medicine     Open Access   (Followers: 3)
Advances in Skeletal Muscle Function Assessment     Open Access  
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
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Advances in Wound Care     Hybrid Journal   (Followers: 11)
Aerospace Medicine and Human Performance     Full-text available via subscription   (Followers: 12)
African Health Sciences     Open Access   (Followers: 3)
African Journal of Biomedical Research     Open Access   (Followers: 1)
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 2)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 2)
African Journal of Trauma     Open Access   (Followers: 1)
Afrimedic Journal     Open Access   (Followers: 2)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AJOB Primary Research     Partially Free   (Followers: 3)
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Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 4)
Al-Azhar Assiut Medical Journal     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 3)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
Althea Medical Journal     Open Access  
American Journal of Biomedical Engineering     Open Access   (Followers: 13)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 7)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 4)
American Journal of Clinical Medicine Research     Open Access   (Followers: 7)
American Journal of Family Therapy     Hybrid Journal   (Followers: 11)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 11)
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American Journal of Medical Case Reports     Open Access   (Followers: 1)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 4)
American Journal of Medicine     Hybrid Journal   (Followers: 48)
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American Journal of Medicine Studies     Open Access   (Followers: 1)
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American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 9)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 5)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 5)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 6)
Anatolian Clinic the Journal of Medical Sciences     Open Access  
Anatomica Medical Journal     Open Access  
Anatomical Science International     Hybrid Journal   (Followers: 3)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy     Open Access   (Followers: 1)
Anatomy Research International     Open Access   (Followers: 2)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Ankara Medical Journal     Open Access   (Followers: 2)
Ankara Üniversitesi Tıp Fakültesi Mecmuası     Open Access  
Annales de Pathologie     Full-text available via subscription  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 2)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 2)
Annals of Bioanthropology     Open Access   (Followers: 4)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 17)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 3)
Annals of Clinical Hypertension     Open Access  
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 12)
Annals of Family Medicine     Open Access   (Followers: 14)
Annals of Health Research     Open Access  
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 7)
Annals of Microbiology     Hybrid Journal   (Followers: 11)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Rehabilitation Medicine     Open Access  
Annals of Saudi Medicine     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 5)
Annual Review of Medicine     Full-text available via subscription   (Followers: 16)
Anthropological Review     Open Access   (Followers: 23)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Technology Journal     Open Access   (Followers: 1)
Antibody Therapeutics     Open Access  
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 3)
Applied Clinical Research, Clinical Trials and Regulatory Affairs     Hybrid Journal  
Applied Medical Informatics     Open Access   (Followers: 12)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access   (Followers: 1)
Archives Medical Review Journal / Arşiv Kaynak Tarama Dergisi     Open Access  
Archives of Asthma, Allergy and Immunology     Open Access  
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 3)
Archives of Medicine and Surgery     Open Access  
Archives of Trauma Research     Open Access   (Followers: 3)
Archivos de Medicina (Manizales)     Open Access  
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access   (Followers: 1)
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access  
Ars Medica : Revista de Ciencias Médicas     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Full-text available via subscription   (Followers: 15)
Arterial Hypertension     Open Access   (Followers: 1)
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 14)
Artificial Organs     Hybrid Journal   (Followers: 1)
ASHA Leader     Open Access  
Asia Pacific Family Medicine     Open Access   (Followers: 1)
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 11)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Biomedicine     Open Access   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 4)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 1)
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Transfusion Science     Open Access   (Followers: 1)
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Cancer Prevention     Open Access  
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 1)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Audiology - Communication Research     Open Access   (Followers: 10)
Auris Nasus Larynx     Full-text available via subscription  
Australian Coeliac     Full-text available via subscription   (Followers: 1)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 1)
Autopsy and Case Reports     Open Access  
Avicenna     Open Access   (Followers: 3)
Avicenna Journal of Clinical Medicine     Open Access  
Avicenna Journal of Medicine     Open Access   (Followers: 1)
Bangabandhu Sheikh Mujib Medical University Journal     Open Access   (Followers: 1)

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Journal Prestige (SJR): 0.931
Citation Impact (citeScore): 3
Number of Followers: 2  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2073-4468
Published by MDPI Homepage  [215 journals]
  • Antibodies, Vol. 7, Pages 15: Hydrophilic Auristatin Glycoside Payload
           Enables Improved Antibody-Drug Conjugate Efficacy and Biocompatibility

    • Authors: Tero Satomaa, Henna Pynnönen, Anja Vilkman, Titta Kotiranta, Virve Pitkänen, Annamari Heiskanen, Bram Herpers, Leo Price, Jari Helin, Juhani Saarinen
      First page: 15
      Abstract: Antibody-drug conjugates (ADCs) offer a combination of antibody therapy and specific delivery of potent small-molecule payloads to target cells. The properties of the ADC molecule are determined by the balance of its components. The efficacy of the payload component increases with higher drug-to-antibody ratio (DAR), while homogeneous DAR = 8 ADCs are easily prepared by conjugation to the four accessible antibody hinge cystines. However, use of hydrophobic payloads has permitted only DAR = 2–4, due to poor pharmacokinetics and aggregation problems. Here, we describe generation and characterization of homogeneous DAR = 8 ADCs carrying a novel auristatin β-D-glucuronide, MMAU. The glycoside payload contributed to overall hydrophilicity of the ADC reducing aggregation. Compared to standard DAR = 2–4 ADCs, cytotoxicity of the homogeneous DAR = 8 ADCs was improved to low-picomolar IC50 values against cancer cells in vitro. Bystander efficacy was restored after ADC internalization and subsequent cleavage of the glycoside, although unconjugated MMAU was relatively non-toxic to cells. DAR = 8 MMAU ADCs were effective against target antigen-expressing xenograft tumors. The ADCs were also studied in 3D in vitro patient-derived xenograft (PDX) assays where they outperformed clinically used ADC. In conclusion, increased hydrophilicity of the payload contributed to the ADC’s hydrophilicity, stability and safety to non-target cells, while significantly improving cytotoxicity and enabling bystander efficacy.
      Citation: Antibodies
      PubDate: 2018-03-22
      DOI: 10.3390/antib7020015
      Issue No: Vol. 7, No. 2 (2018)
  • Antibodies, Vol. 7, Pages 16: Small-Format Drug Conjugates: A Viable
           Alternative to ADCs for Solid Tumours'

    • Authors: Mahendra Deonarain, Gokhan Yahioglu, Ioanna Stamati, Anja Pomowski, James Clarke, Bryan Edwards, Soraya Diez-Posada, Ashleigh Stewart
      First page: 16
      Abstract: Antibody–Drug Conjugates (ADCs) have been through multiple cycles of technological innovation since the concept was first practically demonstrated ~40 years ago. Current technology is focusing on large, whole immunoglobulin formats (of which there are approaching 100 in clinical development), many with site-specifically conjugated payloads numbering 2 or 4. Despite the success of trastuzumab-emtansine in breast cancer, ADCs have generally failed to have an impact in solid tumours, leading many to explore alternative, smaller formats which have better penetrating properties as well as more rapid pharmacokinetics (PK). This review describes research and development progress over the last ~10 years obtained from the primary literature or conferences covering over a dozen different smaller format-drug conjugates from 80 kDa to around 1 kDa in total size. In general, these agents are potent in vitro, particularly more recent ones incorporating ultra-potent payloads such as auristatins or maytansinoids, but this potency profile changes when testing in vivo due to the more rapid clearance. Strategies to manipulate the PK properties, whilst retaining the more effective tumour penetrating properties could at last make small-format drug conjugates viable alternative therapeutics to the more established ADCs.
      Citation: Antibodies
      PubDate: 2018-03-31
      DOI: 10.3390/antib7020016
      Issue No: Vol. 7, No. 2 (2018)
  • Antibodies, Vol. 7, Pages 17: Special Issue: Monoclonal Antibodies

    • Authors: Christian Klein
      First page: 17
      Abstract: Monoclonal antibodies are utilized in clinical practice for the treatment of various diseases including cancer, autoimmunity, metabolic and infectious diseases [...]
      Citation: Antibodies
      PubDate: 2018-04-10
      DOI: 10.3390/antib7020017
      Issue No: Vol. 7, No. 2 (2018)
  • Antibodies, Vol. 7, Pages 2: Myelin Antigens and Antimyelin Antibodies

    • Authors: Fredrick Seil
      First page: 2
      Abstract: The purpose of this review is to provide an historical perspective on studies of serum derived antimyelin antibodies. Antimyelin antibodies can be defined by their action on myelinating organotypic nervous system tissue cultures and include demyelinating antibodies, which have destructive effects on myelin when applied to already myelinated cultures, and myelination inhibiting antibodies, which prevent myelin formation when applied to cultures prior to myelination. Myelin antigens were evaluated in animal studies for their ability to induce experimental allergic encephalomyelitis, an inflammatory demyelinating disease, and correlated with the induction of antimyelin antibodies. As tissue culture demyelinating activity was also found in sera from some patients with multiple sclerosis, a human inflammatory demyelinating disease, studies were undertaken to characterize the nature of the demyelinating factors.
      Citation: Antibodies
      PubDate: 2018-01-02
      DOI: 10.3390/antib7010002
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 3: Tumor-Directed Blockade of CD47 with
           Bispecific Antibodies Induces Adaptive Antitumor Immunity

    • Authors: Elie Dheilly, Stefano Majocchi, Valéry Moine, Gérard Didelot, Lucile Broyer, Sébastien Calloud, Pauline Malinge, Laurence Chatel, Walter Ferlin, Marie Kosco-Vilbois, Nicolas Fischer, Krzysztof Masternak
      First page: 3
      Abstract: CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted with patient safety issues and poor pharmacology due to the widespread CD47 “antigen sink”. A potential solution is tumor-directed blockade of CD47, which can be achieved with bispecific antibodies (biAbs). Using mouse CD47-blocking biAbs in a syngeneic tumor model allowed us to evaluate the efficacy of tumor-directed blockade of CD47 in the presence of the CD47 antigen sink and a functional adaptive immune system. We show here that CD47-targeting biAbs inhibited tumor growth in vivo, promoting durable antitumor responses and stimulating CD8+ T cell activation in vitro. In vivo efficacy of the biAbs could be further enhanced when combined with chemotherapy or PD-1/PD-L1 immune checkpoint blockade. We also show that selectivity and pharmacological properties of the biAb are dependent on the affinity of the anti-CD47 arm. Taken together, our study validates the approach to use CD47-blocking biAbs either as a monotherapy or part of a multi-drug approach to enhance antitumor immunity.
      Citation: Antibodies
      PubDate: 2018-01-03
      DOI: 10.3390/antib7010003
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 4: Enzyme-Based Labeling Strategies for
           Antibody–Drug Conjugates and Antibody Mimetics

    • Authors: Georg Falck, Kristian Müller
      First page: 4
      Abstract: Strategies for site-specific modification of proteins have increased in number, complexity, and specificity over the last years. Such modifications hold the promise to broaden the use of existing biopharmaceuticals or to tailor novel proteins for therapeutic or diagnostic applications. The recent quest for next-generation antibody–drug conjugates (ADCs) sparked research into techniques with site selectivity. While purely chemical approaches often impede control of dosage or locus of derivatization, naturally occurring enzymes and proteins bear the ability of co- or post-translational protein modifications at particular residues, thus enabling unique coupling reactions or protein fusions. This review provides a general overview and focuses on chemo-enzymatic methods including enzymes such as formylglycine-generating enzyme, sortase, and transglutaminase. Applications for the conjugation of antibodies and antibody mimetics are reported.
      Citation: Antibodies
      PubDate: 2018-01-04
      DOI: 10.3390/antib7010004
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 5: Pharmacokinetic and Pharmacodynamic
           Considerations for the Use of Monoclonal Antibodies in the Treatment of
           Bacterial Infections

    • Authors: Shun Wang-Lin, Joseph Balthasar
      First page: 5
      Abstract: Antibiotic-resistant bacterial pathogens are increasingly implicated in hospital- and community-acquired infections. Recent advances in monoclonal antibody (mAb) production and engineering have led to renewed interest in the development of antibody-based therapies for treatment of drug-resistant bacterial infections. Currently, there are three antibacterial mAb products approved by the Food and Drug Administration (FDA) and at least nine mAbs are in clinical trials. Antibacterial mAbs are typically developed to kill bacteria or to attenuate bacterial pathological activity through neutralization of bacterial toxins and virulence factors. Antibodies exhibit distinct pharmacological mechanisms from traditional antimicrobials and, hence, cross-resistance between small molecule antimicrobials and antibacterial mAbs is unlikely. Additionally, the long biological half-lives typically found for mAbs may allow convenient dosing and vaccine-like prophylaxis from infection. However, the high affinity of mAbs and the involvement of the host immune system in their pharmacological actions may lead to complex and nonlinear pharmacokinetics and pharmacodynamics. In this review, we summarize the pharmacokinetics and pharmacodynamics of the FDA-approved antibacterial mAbs and those are currently in clinical trials. Challenges in the development of antibacterial mAbs are also discussed.
      Citation: Antibodies
      PubDate: 2018-01-04
      DOI: 10.3390/antib7010005
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 6: In-Depth Comparison of Lysine-Based
           Antibody-Drug Conjugates Prepared on Solid Support Versus in Solution

    • Authors: Keith Arlotta, Aditya Gandhi, Hsiao-Nung Chen, Christine Nervig, John Carpenter, Shawn Owen
      First page: 6
      Abstract: Antibody drug conjugates are a rapidly growing form of targeted chemotherapeutics. As companies and researchers move to develop new antibody–drug conjugate (ADC) candidates, high-throughput methods will become increasingly common. Here we use advanced characterization techniques to assess two trastuzumab-DM1 (T-DM1) ADCs; one produced using Protein A immobilization and the other produced in solution. Following determination of payload site and distribution with liquid chromatography-mass spectrometry (LC/MS), thermal stability, heat-induced aggregation, tertiary structure, and binding affinity were characterized using differential scanning calorimetry (DSC), dynamic light scattering (DLS), Raman spectroscopy, and isothermal titration calorimetry (ITC), respectively. Small differences in the thermal stability of the CH2 domain of the antibody as well as aggregation onset temperatures were observed from DSC and DLS, respectively. However, no significant differences in secondary and tertiary structure were observed with Raman spectroscopy, or binding affinity as measured by ITC. Lysine-based ADC conjugation produces an innately heterogeneous population that can generate significant variability in the results of sensitive characterization techniques. Characterization of these ADCs indicated nominal differences in thermal stability but not in tertiary structure or binding affinity. Our results lead us to conclude that lysine-based ADCs synthesized following Protein A immobilization, common in small-scale conjugations, are highly similar to equivalent ADCs produced in larger scale, solution-based methods.
      Citation: Antibodies
      PubDate: 2018-01-07
      DOI: 10.3390/antib7010006
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 7: Acknowledgement to Reviewers of Antibodies in

    • Authors: Antibodies Editorial Office
      First page: 7
      Abstract: Peer review is an essential part in the publication process, ensuring that Antibodies maintains high quality standards for its published papers.[...]
      Citation: Antibodies
      PubDate: 2018-01-10
      DOI: 10.3390/antib7010007
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 8: Therapeutic Antibody-Like Immunoconjugates
           against Tissue Factor with the Potential to Treat Angiogenesis-Dependent
           as Well as Macrophage-Associated Human Diseases

    • Authors: Zhiwei Hu
      First page: 8
      Abstract: Accumulating evidence suggests that tissue factor (TF) is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD), endometriosis and rheumatoid arthritis (RA). Macrophage is involved in the progression of a variety of human diseases, such as atherosclerosis and viral infections (human immunodeficiency virus, HIV and Ebola). It is well documented that TF is selectively expressed on angiogenic vascular endothelial cells (VECs) in these pathological angiogenesis-dependent human diseases and on disease-associated macrophages. Under physiology condition, TF is not expressed by quiescent VECs and monocytes but is solely restricted on some cells (such as pericytes) that are located outside of blood circulation and the inner layer of blood vessel walls. Here, we summarize TF expression on angiogenic VECs, macrophages and other diseased cell types in these human diseases. In cancer, for example, the cancer cells also overexpress TF in solid cancers and leukemia. Moreover, our group recently reported that TF is also expressed by cancer-initiating stem cells (CSCs) and can serve as a novel oncotarget for eradication of CSCs without drug resistance. Furthermore, we review and discuss two generations of TF-targeting therapeutic antibody-like immunoconjugates (ICON and L-ICON1) and antibody-drug conjugates that are currently being tested in preclinical and clinical studies for the treatment of some of these human diseases. If efficacy and safety are proven in current and future clinical trials, TF-targeting immunoconjugates may provide novel therapeutic approaches with potential to broadly impact the treatment regimen of these significant angiogenesis-dependent, as well as macrophage-associated, human diseases.
      Citation: Antibodies
      PubDate: 2018-01-23
      DOI: 10.3390/antib7010008
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 9: Structural Changes in Stx1 Engineering
           Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a
           Rapid Latex Agglutination Test

    • Authors: Daniela Luz, Emerson Shiga, Gang Chen, Wagner Quintilio, Fernanda Andrade, Andrea Maranhão, Bruna Caetano, Thaís Mitsunari, Míriam Silva, Letícia Rocha, Ana Moro, Sachdev Sidhu, Roxane Piazza
      First page: 9
      Abstract: Stx1 toxin is one of the AB5 toxins of Shiga toxin-producing Escherichia coli (STEC) responsible for foodborne intoxication during outbreaks. The single-chain variable fragment (scFv) is the most common recombinant antibody format; it consists of both variable chains connected by a peptide linker with conserved specificity and affinity for antigen. The drawbacks of scFv production in bacteria are the heterologous expression, conformation and stability of the molecule, which could change the affinity for the antigen. In this work, we obtained a stable and functional scFv-Stx1 in bacteria, starting from IgG produced by hybridoma cells. After structural modifications, i.e., change in protein orientation, vector and linker, its solubility for expression in bacteria was increased as well as the affinity for its antigen, demonstrated by a scFv dissociation constant (KD) of 2.26 × 10−7 M. Also, it was able to recognize purified Stx1 and cross-reacted with Stx2 toxin by ELISA (Enzyme-Linked Immunosorbent Assay), and detected 88% of Stx1-producing strains using a rapid latex agglutination test. Thus, the scFv fragment obtained in the present work is a bacteria-produced tool for use in a rapid diagnosis test, providing an alternative for STEC diagnosis.
      Citation: Antibodies
      PubDate: 2018-02-01
      DOI: 10.3390/antib7010009
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 10: Factors Affecting the Pharmacology of
           Antibody–Drug Conjugates

    • Authors: Andrew Lucas, Lauren Price, Allison Schorzman, Mallory Storrie, Joseph Piscitelli, Juan Razo, William Zamboni
      First page: 10
      Abstract: Major advances in therapeutic proteins, including antibody–drug conjugates (ADCs), have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS) and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development.
      Citation: Antibodies
      PubDate: 2018-02-07
      DOI: 10.3390/antib7010010
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 11: Challenges in Optimising the Successful
           Construction of Antibody Drug Conjugates in Cancer Therapy

    • Authors: Thomas Mehrling, Daniel Soltis
      First page: 11
      Abstract: Although considerable progress has been made in the field of cancer chemotherapy, there remains a significant unmet medical need, with a requirement to move away from traditional cytotoxics and explore novel, smarter chemotherapeutic approaches. One such example of the smart chemotherapy approach is antibody-drug conjugates (ADCs), which consist of an antibody that binds selectively to a cancer antigen linked to a cytotoxic agent. When developing an ADC, it may be necessary to produce a variety of constructs to fully assess the optimal configuration for the molecule. By testing ADCs prepared using a range of cytotoxic agents, linkers, or different antibodies, it is possible to fully assess the optimal approach for this treatment modality before advancing to the clinic. Since the development and approval of first-generation ADCs, significant improvements in development technology have occurred. Here, we consider the advances made within the field of ADCs, focusing on the development of EDO-B278 and EDO-B776, both of which have demonstrated efficacy in preclinical testing. Although some limitations remain in this field of development, the potential reduction in toxicity offered by ADCs justifies the investment in research to find workable solutions that could ultimately provide patients with superior outcomes.
      Citation: Antibodies
      PubDate: 2018-02-13
      DOI: 10.3390/antib7010011
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 12: A Polar Sulfamide Spacer Significantly
           Enhances the Manufacturability, Stability, and Therapeutic Index of
           Antibody–Drug Conjugates

    • Authors: Jorge Verkade, Marloes Wijdeven, Remon van Geel, Brian Janssen, Sander van Berkel, Floris van Delft
      First page: 12
      Abstract: Despite tremendous efforts in the field of targeted cancer therapy with antibody–drug conjugates (ADCs), attrition rates have been high. Historically, the priority in ADC development has been the selection of target, antibody, and toxin, with little focus on the nature of the linker. We show here that a short and polar sulfamide spacer (HydraSpace™, AE Oss, the Netherland) positively impacts ADC properties in various ways: (a) efficiency of conjugation; (b) stability; and (c) therapeutic index. Different ADC formats are explored in terms of drug-to-antibody ratios (DAR2, DAR4) and we describe the generation of a DAR4 ADC by site-specific attachment of a bivalent linker–payload construct to a single conjugation site in the antibody. A head-to-head comparison of HydraSpace™-containing DAR4 ADCs to marketed drugs, derived from the same antibody and toxic payload components, indicated a significant improvement in both the efficacy and safety of several vivo models, corroborated by in-depth pharmacokinetic analysis. Taken together, HydraSpace™ technology based on a polar sulfamide spacer provides significant improvement in manufacturability, stability, and ADC design, and is a powerful platform to enable next-generation ADCs with enhanced therapeutic index.
      Citation: Antibodies
      PubDate: 2018-02-20
      DOI: 10.3390/antib7010012
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 13: Evaluation of Continuous Membrane
           Chromatography Concepts with an Enhanced Process Simulation Approach

    • Authors: Steffen Zobel-Roos, Dominik Stein, Jochen Strube
      First page: 13
      Abstract: Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-cost alternative to bead-based chromatography with minor drawbacks in terms of capacity. Hence, continuous membrane chromatography should have a high potential. The evaluation of continuous processes goes often along with process modeling. Only few experiments with small feed demand need to be conducted to estimate the model parameters. Afterwards, a variety of different process setups and working points can be analyzed in a very short time, making the approach very efficient. Since the available modeling approaches for membrane chromatography modules did not fit the used design, a new modeling approach is shown. This combines the general rate model with an advanced fluid dynamic distribution. Model parameter determination and model validation were done with industrial cell cultures containing Immunoglobulin G (IgG). The validated model was used to evaluate the feasibility of the integrated Counter Current Chromatography (iCCC) concept and the sequential chromatography concept for membrane adsorber modules, starting with a laboratory-type module used for sample preparation. A case study representing a fed-batch reactor with a capacity from 20 to 2000 L was performed. Compared to batch runs, a 71% higher capacity, 48.5% higher productivity, and 38% lower eluent consumption could be achieved.
      Citation: Antibodies
      PubDate: 2018-03-02
      DOI: 10.3390/antib7010013
      Issue No: Vol. 7, No. 1 (2018)
  • Antibodies, Vol. 7, Pages 14: Infusion Reactions Associated with the
           Medical Application of Monoclonal Antibodies: The Role of Complement
           Activation and Possibility of Inhibition by Factor H

    • Authors: Tamás Fülöp, Tamás Mészáros, Gergely Kozma, János Szebeni, Mihály Józsi
      First page: 14
      Abstract: Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then focus on the reactions caused by mAb therapy. Because the alternative pathway of complement activation may amplify such adverse reactions, we highlight the potential use of complement factor H as an inhibitor of CARPA.
      Citation: Antibodies
      PubDate: 2018-03-14
      DOI: 10.3390/antib7010014
      Issue No: Vol. 7, No. 1 (2018)
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