COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade

Autor: Gady Cojocaru, Margaret L. Tang, Patrick Wall, Sandeep Kumar, Eran Ophir, Hsin-Yuan Cheng, John J. Hunter, Ling Leung, Andrew W. Drake, Maya F. Kotturi, Masha Frenkel, Kathryn Logronio, David Bernados, Moran Galperin, Kyle Hansen, Spencer Liang, Samir Qurashi, Mark A. White, Zoya Alteber, Sarah Whelan
Rok vydání: 2021
Předmět:
Zdroj: Cancer Immunology, Immunotherapy. 70:3525-3540
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-021-02921-8
Popis: 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.
Databáze: OpenAIRE
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