CTLA-4 is a transmembrane surface protein found on the surface of T cells that under normal conditions helps to maintain homeostasis in the immune system by down-regulating the activity of T cells. The CTLA-4 pathway takes effect during the early stage of immune response prior to the PD-1 checkpoint, occurring principally in the lymph nodes when CTLA-4 on activated T cells binds to its ligands B7-1 (CD80) or B7-2 (CD86) on antigen presenting cells or tumor cells. CTLA-4/B7 interaction out-competes the stimulatory receptor CD28 on T cells, leads to attenuated T cell activity. Blockade of immune checkpoints using antibody drugs has been shown to promote T cell activation and proliferation, and stimulate the generation of memory T cells leading to durable anti-tumor response.

Presently, Bristol-Myers Squibb’s Yervoy® (ipilimumab) is the only anti-CTLA-4 antibody on the market, but it has not yet been approved in China. Pre-clinical tests have shown that CS1002 has high affinity to CTLA-4 and is expected to match Yervoy® clinical activity and safety in cancer patients.

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