COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade.
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.
['Hansen|Kyle|K|', 'Kumar|Sandeep|S|', 'Logronio|Kathryn|K|', 'Whelan|Sarah|S|', 'Qurashi|Samir|S|', 'Cheng|Hsin-Yuan|HY|', 'Drake|Andrew|A|', 'Tang|Margaret|M|', 'Wall|Patrick|P|', 'Bernados|David|D|', 'Leung|Ling|L|', 'Ophir|Eran|E|http://orcid.org/0000-0003-3354-0196', 'Alteber|Zoya|Z|', 'Cojocaru|Gady|G|', 'Galperin|Moran|M|', 'Frenkel|Masha|M|', 'White|Mark|M|', 'Hunter|John|J|', 'Liang|Spencer C|SC|', 'Kotturi|Maya F|MF|']
D000818:Animals D000911:Antibodies, Monoclonal D060890:B7-H1 Antigen D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D006801:Humans D007074:Immunoglobulin G D007167:Immunotherapy D019169:Jurkat Cells D008252:Macaca fascicularis D051379:Mice D008807:Mice, Inbred BALB C D011956:Receptors, Cell Surface D011971:Receptors, Immunologic D015398:Signal Transduction
TIGIT PVRIG Checkpoint inhibitors Cancer immunotherapy