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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.^H 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.^P A tumor cell can upregulate PD-L1 expression to mimic normal cells and “turn off” T-cells to escape immune surveillance.^pjm

Blocking the PD-1/PD-L1 signaling pathway by an anti-PD-1 antibody allows T-cells to maintain their effector functions.^A The Fc portion of the anti-PD-1 antibody and its limited interaction with FcγR are important for its therapeutic activities.^O 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.^O

Tislelizumab is a humanized IgG4 mAb with high affinity and binding specificity against PD-1.^U Tislelizumab was specifically engineered to minimize binding to FcγR on macrophages.^O Minimal binding of anti-PD-1 antibodies to FcγR abrogates antibody-dependent cellular phagocytosis, a potential mechanism of T-cell clearance.^lNrll 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%).^z@

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For an exhaustive list of tislelizumab monotherapy and combination clinical trials view the $SvSzKJRS;f V-JH-LK.

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