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T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory immune checkpoint receptor expressed on multiple immune cells, including regulatory T-cells (Tregs), activated and exhausted T-cells, and natural killer (NK) cells.^c

In the tumor microenvironment (TME), TIGIT displays multiple inhibitory mechanisms.^h Highly expressed on Tregs^J, TIGIT signaling enhances their immunosuppressive functions leading to T-cell exhaustion.^k/n When expressed on T-cells and NK-cells, TIGIT binds to two ligands, CD155 (PVR, nectin-like protein-5) and CD112 (PVRL-2, nectin-2), expressed by tumor cells which leads to inhibitory signaling in T-cells and promotes functional exhaustion of tumor-infiltrating lymphocytes.^\S`SN The immune-activating co-stimulatory receptor CD226 (DNAM-1) is also expressed on T-cells and NK-cells. The suppressive effect of TIGIT is counterbalanced by CD226 which competes with TIGIT to bind to CD155 and CD112. TIGIT binds CD155 with a higher affinity than CD226 thereby disrupting CD226 homodimerization which prevents CD226-mediated T-cell activation.^WfZf[

Ociperlimab exerts its effects by multiple mechanisms^Eeh:

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Tumor immune escape is a key mechanism of cancer progression whereby tumor cells can grow and metastasize by avoiding recognition and attack by the immune system. In solid tumors, TIGIT is highly co-expressed with PD-1 on CD8+ T cells. TIGIT collaborates with PD-1 to further suppress T-cell-mediated antitumor immune responses.^h Dual targeting of the TIGIT/CD155/CD112 and PD-1/PD-L1 pathways may overcome tumor immune escape and enhance anti-tumor response in patients with advanced solid tumors.^h

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For an exhaustive list of ociperlimab in combination clinical trials, view the @UgU5/:+U=K %;M1;8o.

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2. Chen X, et al. An Fc-Competent Anti-Human TIGIT Blocking Antibody Ociperlimab (BGB-A1217) Elicits Strong Immune Responses and Potent Anti-Tumor Efficacy in Pre-Clinical Models. Xv3l? lkk2RVA 2022; 22(13):828319.
3. Zhou XM, et al. Intrinsic Expression of Immune Checkpoint Molecule TIGIT Could Help Tumor Growth in vivo by Suppressing the Function of NK and CD8+ T Cells Xv3l? lkk2RVA 2018; 9(2821).
4. Chauvin, J.-M. & Zarour, H. M. TIGIT in cancer immunotherapy. 9. %%%%\Fj%KL. @A]^uc 2020;8, e000957.
5. Joller N, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. |**{+oj[ 2014; 40(4):569-81.
6. Yu X, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. @{j vLLl@vR 2009;10(1):48-57.
7. Joller N, et al. Cutting Edge: TIGIT Has T Cell-Intrinsic Inhibitory Functions. l rffIbW? 2011;186 (3) 1338-1342.
8. Bottino C, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. = yq* |#i 2003;198(4):557-67.
9. Ge Z, et al. TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer. Xv3l? lkk2RVA 2021; 22(12):699895.