PD-1 is an immune inhibitory receptor expressed on activated T cells and B cells, playing a key role in regulating immune responses to tumor antigens and self-antigens. The interaction between PD-1 on adjacent cells and its ligands PD-L1 or PD-L2 inhibits the transmission of the TCR signaling pathway, as well as TCR-mediated cell proliferation, transcription activation, and cytokine production.
PD-L1 monoclonal antibodies are currently the hottest target in immunotherapy. By blocking the interaction between PD-1 on activated T cells and PD-L1 on tumor cells, PD-L1 monoclonal antibodies restore the body's immune cells' ability to effectively recognize tumors. O drug and K drug were approved for marketing in China in June and July 2018, respectively. Subsequently, Junshi Biosciences' Toripalimab and Cindat BioTech's Sintilimab were approved for marketing in December 2018, Henlius' Camrelizumab was approved for marketing in May 2019, BeiGene's Tislelizumab was approved for marketing in December 2019, and in August 2021, Kangfang Biotech's Pyrotinib monoclonal antibody and Yuheng Bio's Selpali monoclonal antibody were successively approved.
PD-L1 monoclonal antibodies have been approved for over twelve types of tumors, making them truly broad-spectrum anti-tumor drugs. However, PD-L1 is not omnipotent and there are primary and acquired resistances, hence combination therapy with chemotherapy, other immune checkpoint inhibitors, monoclonal antibodies, oncolytic viruses, etc., has become an inevitable trend. In addition, to improve response rates, PD-L1 expression levels, microsatellite instability, and tumor mutation burden are important predictive biomarkers for efficacy.