Tislelizumab (BGB-A317) is a humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.1,2

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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.^ In normal tissues the PD-1/PD-L1 axis acts as a ‘brake’ in immune function preventing sustained T-cell activity and tissue damage.% T-cells are activated via binding of the TCR to the MHC/antigen complex on an APC or tumor cell.` Upon T-cell activation, PD-1 expression is induced.s A tumor cell can upregulate PD-L1 expression to mimic normal cells and “turn off” T-cells to escape immune surveillance.+*o

Blocking the PD-1/PD-L1 signaling pathway by an anti-PD-1 antibody allows T-cells to maintain their effector functions.\ The Fc portion of the anti-PD-1 antibody and its limited interaction with FcγR are important for its therapeutic activities.i Activated 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.Anti-PD-1 antibodies, which bind to FcγRs, likely mediate the crosslinking between PD-1+ T cells and FcγR+ macrophages. Such crosslinking could potentially induce macrophages to phagocytize PD-1+ T cells and possibly diminish antitumor responses.i

Tislelizumab is a humanized IgG4 mAb with high affinity and binding specificity against PD-1.Tislelizumab was specifically engineered to minimize binding to FcγR on macrophages.i Minimal binding of anti-PD-1 antibodies to FcγR abrogates antibody-dependent cellular phagocytosis, a potential mechanism of T-cell clearance.8Mc88 Binding 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%).8w


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For an exhaustive list of tislelizumab monotherapy and combination clinical trials view the IL[L6J1kL(0 DWu9Wbi.

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  1. Zhang T et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. OvA{lE =||wuO@ 9\\?^0a%q4. 2018;67:1079–1090.
  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. ,. Y+nBVd. jRIgc. Off. Publ. Int. Assoc. Study Lung Cancer 2021;16:1512–1522.
  3. Ribatti D. The concept of immune surveillance against tumors: The first theories. +FyTrTvX\r 2017; 8:7175-7180.
  4. LaFleur MW, et al. Inhibitors of the PD-1 Pathway in Tumor Therapy. \ ?((?H#` 2018 Jan 15; 200(2):375-383.
  5. Tsai KK et al. PD-1 and PD-L1 antibodies for melanoma. V#4sr [l!!4c9K |fm0| fgg,2_0A5$LC5,0?RU 2014; 10:3111–3116
  6. Mahoney KM et al. The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma mXf:. AQ!v 2015; 37:764–782.
  7. Sznol M. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. ]lN[ =phP,D @@w. 2013;1 9:1021–1034.
  8. Waldman AD, et al. A guide to cancer immunotherapy: from T cell basic science to clinical practice. E_D Qmm IWWEa8z 2020; 20:651-668.
  9. 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). YFF c(L0i 2017; 28(suppl_5):v122–v141.
  10. Arlauckas SP et al. In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy. [PG =SZN[: K-9 2017; 9:eaal3604.
  11. Dahan R et al. FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. At?4H1 ~}TT 2015; 28:285–295.
  12. Hong Y et al. Tislelizumab uniquely binds to the CC0loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage. Iq^? LgoG etV 2021; 11(3):782-792


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