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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.^V In normal tissues the PD-1/PD-L1 axis acts as a ‘brake’ in immune function preventing sustained T-cell activity and tissue damage.^U 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.^t A tumor cell can upregulate PD-L1 expression to mimic normal cells and “turn off” T-cells to escape immune surveillance.^U-{

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.^\ 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.^\

Tislelizumab is a humanized IgG4 mAb with high affinity and binding specificity against PD-1.⁸ Tislelizumab was specifically engineered to minimize binding to FcγR on macrophages.^\ Minimal binding of anti-PD-1 antibodies to FcγR abrogates antibody-dependent cellular phagocytosis, a potential mechanism of T-cell clearance.⁸⁾⁶⁸⁸ 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%).^9y

For an exhaustive list of tislelizumab monotherapy and combination clinical trials view the ca5aYfl(ah# |GmIGF9.

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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. a4txyi KUUXif3 nYY?d0;o8E. 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. C. tjYDCI. qugLt. Off. Publ. Int. Assoc. Study Lung Cancer 2021;16:1512–1522.
3. Ribatti D. The concept of immune surveillance against tumors: The first theories. #A8Wz5glvz 2017; 8:7175-7180.
4. LaFleur MW, et al. Inhibitors of the PD-1 Pathway in Tumor Therapy. # SOOU*XF 2018 Jan 15; 200(2):375-383.
5. Tsai KK et al. PD-1 and PD-L1 antibodies for melanoma. o%?g7 /ZEEXTc/ o/Ivn |66K(TpsnS@jnKpTi! 2014; 10:3111–3116
6. Mahoney KM et al. The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma ,sI|. IglF 2015; 37:764–782.
7. Sznol M. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. ab$s q!WalY 7fL. 2013;1 9:1021–1034.
8. Waldman AD, et al. A guide to cancer immunotherapy: from T cell basic science to clinical practice. nIT D16 O;;Hi1R 2020; 20:651-668.
9. Desai J et al. Preliminary results from subsets of patients (pts) with advanced gastric cancer (GC) and esophageal carcinoma (EC) in a dose-escalation/expansion study of BGB-A317, an anti-PD-1 monoclonal antibody (mAb). Mgg vEhAS 2017; 28(suppl_5):v122–v141.
10. Arlauckas SP et al. In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy. A,* bW,r9( UD5 2017; 9:eaal3604.
11. Dahan R et al. FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. 8$Kpy\ _A:: 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. %Q&X eB1! 9}[ 2021; 11(3):782-792