COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or...

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Immune checkpoint inhibitors (ICIs) like PD-(L)1 and CTLA-4 offer cancer treatment benefits but have limited efficacy in some patients.
• TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor that can limit anti-tumor immune responses.
• PVR (poliovirus receptor, CD155) is the cognate ligand for TIGIT, and their interaction suppresses T cell activity.

Purpose of the Study:

• To evaluate the expression of TIGIT and PVR in various human solid tumors.
• To develop and assess the therapeutic potential of COM902, a novel anti-TIGIT antibody.
• To investigate the efficacy of COM902 as a monotherapy and in combination with other immunotherapies.

Main Methods:

• Assessed TIGIT and PVR expression in a large cohort of human solid tumors and normal tissues.
• Generated COM902, a human IgG4 monoclonal antibody targeting TIGIT, with cross-reactivity to human, cynomolgus, and mouse TIGIT.
• Evaluated COM902's ability to block TIGIT-PVR interaction and enhance antigen-specific T cell responses in vitro.
• Tested in vivo efficacy of a chimeric COM902 in combination with anti-PVRIG or anti-PD-L1 antibodies in syngeneic mouse tumor models.

Main Results:

• TIGIT was found to be expressed on CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and upregulated in tumors compared to normal tissues.
• PVR was expressed on tumor cells and tumor-associated macrophages across multiple solid tumors.
• COM902 demonstrated in vitro enhancement of antigen-specific T cell responses when used alone or with COM701 (anti-PVRIG) or a PD-1 inhibitor.
• In vivo studies showed that COM902 in combination with anti-PVRIG or anti-PD-L1 antibodies significantly inhibited tumor growth and improved survival in mouse models.

Conclusions:

• TIGIT and PVR are widely expressed in human solid tumors, suggesting their potential as therapeutic targets.
• COM902 effectively targets TIGIT, blocks its interaction with PVR, and enhances anti-tumor immune responses.
• COM902, particularly in combination therapies, represents a promising therapeutic candidate for advanced malignancies.