In addition to anti-PD-1, immunoresuppressors can also be suppressed by phosphatase collection

antagonists that interact with extracellular-mediates can inhibit the signaling of cell surface subjects and are widely used in the treatment of a variety of diseases, including tumors. For example, the regulation of T-cell signals by co-subjects such as PD-1 and CTLA-4 has been key to tumor immunotherapy. The subject phosphatation is regulated by several processes, including reverse regulation of phosphatases such as CD45.Anti-PD-1 antibodies effectively block the signaling of the mating body activation, but they do not inhibit the continuous intracellular PD-1 signaling, which continuously inhibits T-cell function.On October 21, 2020, Nature published the journal K. Christopher Garcia's team called the Immune Receptor reedion through phosphatase adrenaline, which found that inhibiting receptors collected by phosphatase enhanced T-cell activity and significantly improved small cell lung and colon adenocarcinoma.
, the researchers used anti-CD3 to reseal Jurkat T cells and observed that CD69 and CD25 increased by about 50 percent in the absence of PD-1. In contrast, the PD-1 over-expression inhibits the CD69 upward. In addition, PD-1 phosphatization can be detected in PD-1 transductive resting Jurkat T cells.CD45 is a compositional active cell surface tyrosine phosphatase, and has a larger extracellular domain (ECD), using anti-CD45 antibodies and dual-specific molecules selectively binding to the ECD of PD-1. The researchers designed a heterogeneic dual-specific bicodesic antibody that binds to CD45 and PD-1 ECD, allowing PD-1 and CD45 to bind to the surface of T cells (RIPR-PD1). The results show that RIPR-PD1 can enhance T cell activity.In addition, in mouse models of small cell lung cancer and colon cancer, MICE-PD1 alone or in combination with chemotherapy drugs increased the proportion of effect memory T cells in the near end of the tumor and the far end of the tumor lymph nodes, and inhibited tumor progression.All in all, the study suggests an alternative way to weaken the signaling of cell surface subjects, called inhibiting them through phosphatase collection (RIPR). In addition, the researchers designed RIPR-PD1, which induces crosslinking between PD-1 and CD45, inhibits signaling of complement and match activation, and has significant anti-tumor effect in mouse tumor models.Different types of cells express different cell surface phosphatase, RIPR method is expected to be used as a tool for the suppression of a variety of kinase-specific ligands, opening up a new direction for the treatment of a variety of diseases. (Biological Exploration):1. Immune Receptor resedion through enforced phosphatase