Pages: 75 - 75 Abstract: We would like to take this opportunity to express our sincere appreciation for those who reviewed manuscripts for our journal Antibody Therapeutics. The valuable insights and feedback from our reviewers are essential in maintaining the high standards of our journal for serving the scientific community. PubDate: Fri, 24 Mar 2023 00:00:00 GMT DOI: 10.1093/abt/tbad005 Issue No:Vol. 6, No. 2 (2023)
Pages: 76 - 86 Abstract: BackgroundRapid and efficient strategies are needed to discover neutralizing antibodies (nAbs) from B cells derived from virus-infected patients.MethodsHere, we report a high-throughput single-B-cell cloning method for high-throughput isolation of nAbs targeting diverse epitopes on the SARS-CoV-2-RBD (receptor binding domain) from convalescent COVID-19 patients. This method is simple, fast and highly efficient in generating SARS-CoV-2-neutralizing antibodies from COVID-19 patients’ B cells.ResultsUsing this method, we have developed multiple nAbs against distinct SARS-CoV-2-RBD epitopes. CryoEM and crystallography revealed precisely how they bind RBD. In live virus assay, these nAbs are effective in blocking viral entry to the host cells.ConclusionThis simple and efficient method may be useful in developing human therapeutic antibodies for other diseases and next pandemic. PubDate: Fri, 17 Feb 2023 00:00:00 GMT DOI: 10.1093/abt/tbad002 Issue No:Vol. 6, No. 2 (2023)
Pages: 87 - 96 Abstract: Aberrant post-translational glycosylation is a well-established hallmark of cancer. Altered core fucosylation mediated by α-(1,6)-fucosyltransferase (Fut8) is one of the key changes in tumor glycan patterns that contributes to neoplastic transformation, tumor metastasis, and immune evasion. Increased Fut8 expression and activity are associated with many types of human cancers, including lung, breast, melanoma, liver, colorectal, ovarian, prostate, thyroid, and pancreatic cancer. In animal models, inhibition of Fut8 activity by gene knockout, RNA interference, and small analogue inhibitors led to reduced tumor growth/metastasis, downregulation of immune checkpoint molecules PD-1, PD-L1/2, and B7-H3, and reversal of the suppressive state of tumor microenvironment. Although the biologics field has long benefited tremendously from using FUT8−/− Chinese hamster ovary cells to manufacture IgGs with greatly enhanced effector function of antibody-dependent cellular cytotoxicity for therapy, it is only in recent years that the roles of Fut8 itself in cancer biology have been studied. Here, we summarize the pro-oncogenic mechanisms involved in cancer development that are regulated by Fut8-mediated core fucosylation, and call for more research in this area where modifying the activity of this sole enzyme responsible for core fucosylation could potentially bring rewarding surprises in fighting cancer, infections, and other immune-related diseases. PubDate: Thu, 02 Mar 2023 00:00:00 GMT DOI: 10.1093/abt/tbad004 Issue No:Vol. 6, No. 2 (2023)
Pages: 97 - 107 Abstract: Background: Ending the global COVID-19 pandemic requires efficacious therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, the emerging Omicron sublineages largely escaped the neutralization of current authorized monoclonal antibody therapies. Here we report a tetravalent bispecific antibody ISH0339, as a potential candidate for long-term and broad protection against COVID-19.Methods: We report here the making of ISH0339, a novel tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life. We describe the preclinical characterization of ISH0339 and discuss its potential as a novel agent for both prophylactic and therapeutic purposes against SARS-CoV-2 infection.Results: ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile.Conclusion: ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs. Investigational New Drug studies to evaluate the safety, tolerability and preliminary efficacy of ISH0339 for both prophylactic and therapeutic purposes against SARS-CoV-2 infection have been filed. PubDate: Mon, 06 Mar 2023 00:00:00 GMT DOI: 10.1093/abt/tbad003 Issue No:Vol. 6, No. 2 (2023)
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