Science: CD28 bispecific antibody can enhance the anti-tumor ability of CD3 bispecific antibody

January 18, 2020 / BIOON / - -- bispecific antibody can help T cells recognize and eliminate cancer cells It has two arms: one that binds to cancer cell antigens and the other to CD3 on the surface of T cells However, bispecific antibodies are not always sufficient to activate T cells T cell activation is initiated when the T cell receptor (TCR) / CD3 complex binds to the peptide major histocompatibility complex (MHC) ("signal 1"); this activation can be enhanced by binding to a second "costimulatory" receptor, such as the CD28 receptor on the T cell surface that binds to a homologous ligand ("signal 2") on the target cell surface CD3 based bispecific antibodies work by replacing conventional signal 1: one arm binds tumor specific antigen (TSA) and the other arm binds TCR / CD3, which makes T cells connect with tumor cells Although some of the so-called tsaxcd3 bispecific antibodies have shown promising antitumor efficacy in cancer patients, their activity remains to be optimized In a new study, researchers from regeneron pharmaceuticals introduced a new class of bispecific antibodies that mimic signal 2 by bridging TSA with costimulatory receptor CD28 on the surface of T cells The related research results were recently published in the Journal of Science Translational Medicine, and the title of the paper was "a class of costimulation CD28 bispecific antibodies that enhances the activity of CD3 bispecific antibodies" Picture from Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aaw7888 They call them tsaxcd28 bispecific antibodies and describe two such bispecific antibodies: one tsaxcd28 bispecific antibody is specific for ovarian cancer antigen, and the other tsaxcd28 bispecific antibody is specific for prostate cancer antigen Unlike the CD28 super agonist, which extensively activates T cells and causes significant side effects in early clinical trials, these tsaxcd28 bispecific antibodies show limited activity and no side effects when used alone in genetically humanized mouse models of immune function or primates However, when used in combination with tsaxcd3 bispecific antibodies, these tsaxcd28 bispecific antibodies can enhance the artificial synapse between T cells and their target cells, enhance the activation of T cells, and significantly improve the antitumor activity of tsaxcd3 bispecific antibodies in a variety of allogeneic and homogeneic tumor models, and show no toxic and side effects Therefore, the combination of this kind of tsaxcd28 bispecific antibody with the emerging tsaxcd3 bispecific antibody may provide ready-made antibody therapy with good tolerance and strong anti-tumor effect (Bio Valley Com) reference: Dimitris skokos et al A class of costimulation CD28 specific antibodies that enhance the ANTIUMOR activity of CD3 specific antibodies Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aaw7888