Science Sub-journal: CD28 double resistance enhances PD-1 anti-tumor effect and does not induce cytokine storms.

The emergence of monoclonal antibody drugs that block PD-1 immune checkpoint has completely changed cancer immunotherapy.although cancer immunotherapy has gained more and more attention in cancer treatment, these methods are not perfect, many cancer patients still do not respond to immunotherapy, and even in the types of reactive tumors, most patients still do not produce sustained anti-tumor immunity.one method of immunotherapy for cancer is bispecific antibodies, which recognize T cell surface receptors and tumor specific antigen (TSA), and help to bring the two types of cells together and activate T cells.on January 8, 2020, regenerant published a paper in the journal Science Translational Medicine, indicating that CD28 double antibody can enhance the anti-tumor effect of CD3 double antibody.in animal experiments, costimulatory CD28 double antibody significantly enhanced the efficacy of CD3 double antibody, and there was no risk of cytokine storm.this study shows that TSA × CD3 bispecific antibody has a great application prospect in the immunotherapy of cancer.on June 24, 2020, regenerant was released in Science Translational This time, Regent has developed a new costimulatory bispecific antibody, TSA × CD28, and confirmed that tsaxcd28 bispecific antibody can synergize with a wider range of anti-PD-1 antibodies, enhance the therapeutic effect of anti-PD-1 antibody, and give better reactivity and long-term immune memory. Moreover, in mouse and primate animal models, tsax-cd28 bispecific antibody can enhance the therapeutic effect of anti-PD-1 antibody, and give better reactivity and long-term immune memory There was no significant toxic effect when TSA × CD28 was used alone or in combination with PD-1 inhibitor,.therefore, the dual antibody can be combined with the existing PD-1 immunotherapy to enhance the therapeutic effect of cancer and induce long-term anti-tumor immunity without inducing cytokine storm.in view of the importance of this study, this paper was selected as the current cover article.cover picture interpretation: CD28 bispecific antibody makes tumor cells and T cells cross-linked, and immune checkpoint inhibitors can prevent T cells from inactivation, thus promoting the killing of tumor cells.TSA × CD28 bispecific antibody enhanced the ability of PD-1 inhibitor to induce T cell activation in vitro.in the humanized mouse model and cynomolgus monkey model, the use of TSA × CD28 bispecific antibody alone or in combination with anti PD-1 monoclonal antibody did not induce systemic T cell activation and cytokine storm.in general, the combination of TSA × CD28 bispecific antibody and PD-1 inhibitor can enhance the anti-tumor effect of PD-1 inhibitor and induce long-term anti-tumor immunity.this study also showed that TSA × CD28 bispecific antibody was different from CD28 super agonist in nature, and could not induce cytokine storm and had good tolerance.blocking the immune checkpoint PD-1 with monoclonal antibodies can release the brake of T cell activation and reactivate tumor immunity. However, for most tumors, the efficacy of PD-1 / PD-L1 monoclonal antibody as a single drug may not be enough to achieve tumor clearance and lasting anti-tumor inhibition.TSA × CD28 bispecific antibody of regenerant combined with PD-1 inhibitor can not only enhance the anti-tumor effect of the latter, but also provide lasting anti-tumor immunity, and has no toxic effect and stronger tolerance.at present, some characteristic technology platforms have emerged in the domestic research and development of bispecific antibodies. The following is the domestic acceptance of bispecific antibodies (as of January 2020).photo source: biopharmaceutical papers link: