{"id":6836,"date":"2024-12-06T12:19:10","date_gmt":"2024-12-06T11:19:10","guid":{"rendered":"https:\/\/beigen.vipdev.lndo.site\/us\/?post_type=compound&p=6836"},"modified":"2025-05-28T11:16:10","modified_gmt":"2025-05-28T09:16:10","slug":"tislelizumab","status":"publish","type":"compound","link":"https:\/\/beonemedaffairs.com\/us\/compound\/6836\/tislelizumab\/","title":{"rendered":"Tislelizumab"},"content":{"rendered":"","protected":false},"template":"","meta":{"_acf_changed":false,"editor_notices":[]},"post-tag":[538],"class_list":["post-6836","compound","type-compound","status-publish","hentry","post-tag-tislelizumab","disease_state-advanced-solid-tumors","disease_state-classical-hodgkins-lymphoma","disease_state-esophageal-cancer","disease_state-esophageal-squamous-cell-carcinoma","disease_state-gastric-cancer","disease_state-gastic-gastroesophageal-junction-cancer","disease_state-hepatocellular-carcinoma","disease_state-nasopharyngeal-cancer","disease_state-non-small-cell-lung-cancer","disease_state-small-cell-lung-cancer","molecule-tislelizumab"],"acf":{"header_text":"Tislelizumab is a humanized IgG4 monoclonal antibody designed to bind and inhibit PD-1.","summary":"Tislelizumab is a humanized IgG4 monoclonal antibody designed to bind and inhibit PD-1.","tags":[538],"text":"","approval_status_for_filter":"approved","accordion_presentation":"expanded","overview":"Tislelizumab (BGB-A317) is a humanized IgG4 anti\u2013PD-1 monoclonal antibody specifically designed to minimize binding to Fc\u03b3R on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.1,2<\/sup>\r\n\r\nTislelizumab is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of solid tumor and hematologic cancers. BeiGene has initiated or completed over 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and 4 pivotal Phase 2 trials.\r\n\r\nReferences <\/strong>\r\n
    \r\n \t
  1. Zhang T et al. The binding of an anti-PD-1 antibody to Fc\u03b3R\u0399 has a profound impact on its biological functions.\u00a0Cancer Immunol Immunother<\/em>. 2018;67:1079\u20131090.<\/li>\r\n \t
  2. Lu, S. et al. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.\u00a0 Thorac. Oncol.<\/em>2021;16:1512\u20131522.<\/li>\r\n<\/ol>","mechanism_of_action":"Immune surveillance is a mechanism by which the immune system identifies cancer cells and eliminates them via cytotoxic T-cells (CTLs). Tumors have developed strategies to escape immune surveillance including an altered expression of various immune checkpoints leading to the suppression of CTL function.1<\/sup>\u00a0In normal tissues the PD-1\/PD-L1 axis acts as a \u2018brake\u2019 in immune function preventing sustained T-cell activity and tissue damage.2<\/sup>\u00a0T-cells are activated via binding of the TCR to the MHC\/antigen complex on an APC or tumor cell.3<\/sup>\u00a0Upon T-cell activation, PD-1 expression is induced.4<\/sup>\u00a0A tumor cell can upregulate PD-L1 expression to mimic normal cells and \u201cturn off\u201d T-cells to escape immune surveillance.3,<\/sup>4<\/sup>\r\n\r\nBlocking the PD-1\/PD-L1 signaling pathway by an anti-PD-1 antibody allows T-cells to maintain their effector functions.5<\/sup>\u00a0The Fc portion of the anti-PD-1 antibody and its limited interaction with Fc\u03b3R are important for its therapeutic activities.6<\/sup>\u00a0Activated tumor-specific T-cells mediate the destruction of tumor cells and secrete cytokines that activate and recruit other immune cells to participate in the antitumor response.7\u00a0<\/sup>Anti-PD-1 antibodies, which bind to Fc\u03b3Rs, likely mediate the crosslinking between PD-1+ T cells and Fc\u03b3R+ macrophages. Such crosslinking could potentially induce macrophages to phagocytize PD-1+ T cells and possibly diminish antitumor responses.6<\/sup>\r\n\r\nTislelizumab is a humanized IgG4 mAb with high affinity and binding specificity for PD-1.8\u00a0<\/sup>Tislelizumab was specifically engineered to minimize binding to Fc\u03b3R on macrophages.6<\/sup>\u00a0Minimal binding of anti-PD-1 antibodies to Fc\u03b3R abrogates antibody-dependent cellular phagocytosis, a potential mechanism of T-cell clearance.9,10<\/sup>\u00a0Binding surface of tislelizumab on PD-1 overlapped largely with that of PD-L1, leading to the complete blockade of PD-1\/PD-L1 interaction (>99%).1<\/sup>1<\/sup>\r\n\r\n\"\"\r\n\r\nReferences<\/strong>\r\n
      \r\n \t
    1. Zhang T et al. The binding of an anti-PD-1 antibody to Fc\u03b3R\u0399 has a profound impact on its biological functions.\u00a0Cancer Immunol Immunother<\/em>. 2018;67:1079\u20131090.<\/li>\r\n \t
    2. Lu, S. et al. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.\u00a0 Thorac. Oncol.<\/em>2021;16:1512\u20131522.<\/li>\r\n \t
    3. Ribatti D. The concept of immune surveillance against tumors: The first theories.\u00a0Oncotarget<\/em>2017; 8:7175-7180.<\/li>\r\n \t
    4. LaFleur MW, et al. Inhibitors of the PD-1 Pathway in Tumor Therapy.\u00a0J Immunol<\/em>2018 Jan 15; 200(2):375-383.<\/li>\r\n \t
    5. Tsai KK et al. PD-1 and PD-L1 antibodies for melanoma.\u00a0Human Vaccines & Immunotherapeutics<\/em>2014; 10:3111\u20133116<\/li>\r\n \t
    6. Zhang T et al. The binding of an anti-PD-1 antibody to Fc\u03b3R\u0399 has a profound impact on its biological functions.\u00a0Cancer Immunol Immunother<\/em>. 2018;67:1079\u20131090.<\/li>\r\n \t
    7. Mahoney KM et al. The Next Immune-Checkpoint Inhibitors: PD-1\/PD-L1 Blockade in Melanoma\u00a0 Ther<\/em>2015; 37:764\u2013782.<\/li>\r\n \t
    8. Sznol M. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer.\u00a0Clin Cancer Res.<\/em>2013;1 9:1021\u20131034.<\/li>\r\n \t
    9. Waldman AD, et al. A guide to cancer immunotherapy: from T cell basic science to clinical practice.\u00a0Nat Rev Immunol<\/em>2020; 20:651-668.<\/li>\r\n \t
    10. Desai J et al. Preliminary results from subsets of patients (pts) with advanced gastric cancer (GC) and esophageal carcinoma (EC) in a dose-escalation\/expansion study of BGB-A317, an anti-PD-1 monoclonal antibody (mAb).\u00a0Ann Oncol\u00a0<\/em>2017; 28(suppl_5):v122\u2013v141.<\/li>\r\n \t
    11. Arlauckas SP et al. In vivo imaging reveals a tumor-associated macrophage\u2013mediated resistance pathway in anti\u2013PD-1 therapy.\u00a0Sci Transl Med\u00a0<\/em>2017; 9:eaal3604.<\/li>\r\n<\/ol>","approval_status":"Tislelizumab is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.\r\n\r\nPlease see<\/em> the full<\/em> US Prescribing Information<\/em><\/strong><\/a> for important information on approved uses.<\/em>\r\n\r\nFor a complete list of tislelizumab monotherapy and combination clinical trials, view the\u00a0pipeline<\/a><\/strong>.","other_resources":[6740,936,7218]},"_links":{"self":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/compound\/6836","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/compound"}],"about":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/types\/compound"}],"acf:post":[{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/posts\/7218"},{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/posts\/936"},{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/posts\/6740"}],"acf:term":[{"embeddable":true,"taxonomy":"post-tag","href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/post-tag\/538"}],"wp:attachment":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/media?parent=6836"}],"wp:term":[{"taxonomy":"post-tag","embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/post-tag?post=6836"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}