COM902，一种靶向 TIGIT 的新型治疗性抗体，与 PVRIG 或 PD-1 通路阻断联合使用时增强抗肿瘤 T 细胞功能

Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer.

However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor and member of the DNAM-1 family of immune modulating proteins.

We evaluated the prevalence of TIGIT and its cognate ligand, PVR (CD155), in human cancers by assessing their expression in a large set of solid tumors. TIGIT is expressed on CD4 + and CD8 + TILs and is upregulated in tumors compared to normal tissues. PVR is expressed on tumor cells and tumor-associated macrophages from multiple solid tumors.

We explored the therapeutic potential of targeting TIGIT by generating COM902, a fully human anti-TIGIT hinge-stabilized IgG4 monoclonal antibody that binds specifically to human, cynomolgus monkey, and mouse TIGIT, and disrupts the binding of TIGIT with PVR. COM902, either alone or in combination with a PVRIG (COM701) or PD-1 inhibitor, enhances antigen-specific human T cell responses in-vitro.

In-vivo, a mouse chimeric version of COM902 in combination with an anti-PVRIG or anti-PD-L1 antibody inhibited tumor growth and increased survival in two syngeneic mouse tumor models. In summary, COM902 enhances anti-tumor immune responses and is a promising candidate for the treatment of advanced malignancies.