{"id":1699,"date":"2022-05-06T14:20:07","date_gmt":"2022-05-06T13:20:07","guid":{"rendered":"https:\/\/beigen.vipdev.lndo.site\/?post_type=compound&#038;p=1699"},"modified":"2024-04-24T14:52:58","modified_gmt":"2024-04-24T13:52:58","slug":"ociperlimab","status":"publish","type":"compound","link":"http:\/\/beonemedaffairs.com\/begenius\/compound\/1699\/ociperlimab\/","title":{"rendered":"Ociperlimab"},"content":{"rendered":"","protected":false},"template":"","meta":{"_acf_changed":false,"editor_notices":[]},"post-tag":[212],"class_list":["post-1699","compound","type-compound","status-publish","hentry","post-tag-ociperlimab-moa"],"acf":{"header_text":"","summary":"Ociperlimab (BGB-A1217) is an investigational humanized monoclonal antibody designed to bind to TIGIT with high specificity and affinity. Ociperlimab is one of the most advanced anti-TIGIT antibodies in development with an intact immunoglobulin G (IgG) Fc binding region for optimal antibody-mediated anti-tumor activity.<sup>1,2<\/sup>\r\n\r\n&nbsp;\r\n\r\n&nbsp;","tags":[212],"text":"<h4><strong>Mode of Action<\/strong><\/h4>\r\nT-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.<sup>3<\/sup>\r\n\r\nIn the tumor microenvironment (TME), TIGIT displays multiple inhibitory mechanisms.<sup>4<\/sup> Highly expressed on Tregs<sup>5<\/sup>, TIGIT signaling enhances their immunosuppressive functions leading to T-cell exhaustion.<sup>4,5 <\/sup>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.<sup>4,6,7<\/sup> 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.<sup>4,8,9<\/sup>\r\n\r\nOciperlimab exerts its effects by multiple mechanisms<sup>1,2<\/sup>:\r\n<ul>\r\n \t<li>Binding of ociperlimab to TIGIT led to a reduction of Tregs by inducing potential antibody-dependent cellular cytotoxicity, but not a reduction in cytotoxic T-cells.<\/li>\r\n \t<li>Ociperlimab blocked the interaction between TIGIT and CD155 and CD112 on tumor cells and increased ligand availability for the CD226 co-stimulatory receptor resulting in reactivation of T-cells and NK cells and anti-tumor immune responses.<\/li>\r\n \t<li>TIGIT expression was reduced on T-cell surfaces through Fc-dependent trogocytosis, while CD226 was upregulated in a Fc-dependent manner.<\/li>\r\n \t<li>Fc\/Fc\u04afR engagement resulted in a proinflammatory TME through myeloid cell and NK-cell activation.<\/li>\r\n<\/ul>\r\nTumor 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.<sup>4<\/sup> 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.<sup>4<\/sup>\r\n\r\n<img class=\"wp-image-5669 size-full\" src=\"https:\/\/beonemedaffairs.com\/wp-content\/uploads\/2022\/05\/Ociperlimab_Compound_V2.jpg\" alt=\"Ociperlimab_Compound_V2\" width=\"4000\" height=\"4000\" \/>\r\n<h4><strong>Ociperlimab in clinical trials <\/strong><\/h4>\r\nOciperlimab is currently being investigated in a pivotal global Phase 3 trial in combination with tislelizumab (anti-PD-1) in first-line (1L) PD-L1 positive advanced\/metastatic non-small cell lung cancer (NSCLC) and in a global Phase 3 trial in locally advanced NSCLC in combination with concurrent chemoradiation. Ociperlimab plus tislelizumab is further investigated in pivotal global Phase 2 trials in combination with chemotherapy in 1L NSCLC irrespective of PD-L1 expression as well as in combination with tislelizumab and concurrent chemoradiotherapy in previously untreated limited-stage small cell lung cancer (LS-SCLC).\r\n\r\nFor an exhaustive list of ociperlimab in combination clinical trials, view the <a href=\"https:\/\/beonemedaffairs.com\/pipeline\/pipeline\/\">development program<\/a>.\r\n\r\n<em>Ociperlimab is not authorized for use in the EU.\u00a0<\/em>\r\n<h4><strong>References <\/strong><\/h4>\r\n<ol>\r\n \t<li>Chen, et al. AACR 2021, Abstract 1854.<\/li>\r\n \t<li>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. <em>Front Immunol<\/em> 2022; 22(13):828319.<\/li>\r\n \t<li>Zhou XM, et al. Intrinsic Expression of Immune Checkpoint Molecule TIGIT Could Help Tumor Growth\u00a0in vivo\u00a0by Suppressing the Function of NK and CD8+\u00a0T Cells <em>Front Immunol<\/em> 2018; 9(2821).<\/li>\r\n \t<li>Chauvin, J.-M. &amp; Zarour, H. M. TIGIT in cancer immunotherapy. <em>J. Immunother. Cancer<\/em> 2020;8, e000957.<\/li>\r\n \t<li>Joller N, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. <em>Immunity<\/em> 2014; 40(4):569-81.<\/li>\r\n \t<li>Yu X, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. <em>Nat Immunol<\/em> 2009;10(1):48-57.<\/li>\r\n \t<li>Joller N, et al. Cutting Edge: TIGIT Has T Cell-Intrinsic Inhibitory Functions. <em>J Immunol<\/em> 2011;186\u00a0(3)\u00a01338-1342.<\/li>\r\n \t<li>Bottino C, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. <em>J Exp Med<\/em> 2003;198(4):557-67.<\/li>\r\n \t<li>Ge Z, et al. TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer. <em>Front Immunol<\/em> 2021; 22(12):699895.<\/li>\r\n<\/ol>","approval_status_for_filter":"","accordion_presentation":"expanded","overview":"","mechanism_of_action":"","approval_status":"","other_resources":null},"_links":{"self":[{"href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/compound\/1699","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/compound"}],"about":[{"href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/types\/compound"}],"acf:term":[{"embeddable":true,"taxonomy":"post-tag","href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/post-tag\/212"}],"wp:attachment":[{"href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/media?parent=1699"}],"wp:term":[{"taxonomy":"post-tag","embeddable":true,"href":"http:\/\/beonemedaffairs.com\/begenius\/wp-json\/wp\/v2\/post-tag?post=1699"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}