Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy

Blake, Stephen J., Dougall, William C., Miles, John J., Teng, Michele W.L., and Smyth, Mark J. (2016) Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy. Clinical Cancer Research, 22 (21). pp. 5183-5188.

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The receptors CD96 and TIGIT are expressed on the surface of T and NK cells and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96-/- mice displaying hypersensitive NK cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK cell-mediated cytotoxicity. TIGIT is also upregulated on T-cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased Treg suppression. The counterbalance between the putative inhibitory CD96, TIGIT receptors and the activating receptor, CD226, offers unique strategies for immuno-oncology drug development. Blocking CD96 or TIGIT with monoclonal antibodies (mAbs) has been shown to improve tumor control in mice, in particular when used in combination with PD-1/PD-L1 blockade. These results have highlighted these pathways as promising new targets for immune modulation. This review will examine the rationale behind targeting CD96 and TIGIT and discuss the potential approaches in translating these preclinical findings into novel clinical agents.

Item ID: 45927
Item Type: Article (Research - C1)
ISSN: 1557-3265
Funders: National Health and Medical Research Council of Australia (NHMRC), Cancer Council Queensland (CCQ), Cancer Research Institute (CRI)
Projects and Grants: NHMRC Project Grant 1088960, NHMRC Development Grant 1093566, CCQ Project Grant 1083776, CRI CLIP Grant, NHMRC 1078671
Date Deposited: 30 Oct 2016 22:23
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320402 Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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