Tislelizumab - Mode of Action
Tislelizumab (BGB-A317) is an investigational humanized IgG4 monoclonal antibody designed to bind to and inhibit PD‑1; a cell surface receptor that plays an important role in allowing tumor cells to evade the immune system.
Many types of cancer cells have hijacked the PD‑L1 expression system that normally exists in healthy cells. By expressing PD‑L1, cancer cells can interact with PD‑1 expressing cytotoxic T‑lymphocytes, or CTLs and protect themselves from being killed by these CTLs, Tislelizumab can potentially restore the ability of CTLs to kill cancer cells by binding to PD‑1, without activating the receptor; thereby preventing PD‑L1 from engaging PD‑1.
Tislelizumab (BGB-A317) is specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.
Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
Tislelizumab is in pivotal Phase 3 and Phase 2 clinical trials in solid tumors and hematologic cancers, including a pivotal Phase 2 clinical trial in relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL). It is also being studied in global Phase 3 trials in a number of malignancies, including non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, as well as two global Phase 2 trials in patients with previously treated hepatocellular carcinoma or with R/R mature T- and NK-cell lymphomas, and an additional pivotal Phase 2 trial in China in urothelial cancer.