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40E4 mIgG1 (D265A) is a preclinical, effector function-reduced (Fc-silent) murine monoclonal antibody that acts as a first-in-class antagonist of B and T Lymphocyte Attenuator (BTLA), an inhibitory co-receptor on T cells. It was specifically engineered to block the BTLA:HVEM (herpesvirus entry mediator) interaction in BALB/c strain mice. The D265A mutation in the IgG1 Fc region eliminates unwanted cytolytic effector functions, making it suitable for in vivo use. In preclinical studies, it demonstrated improved tumor growth inhibition in mouse models of breast cancer (EMT6) and colon cancer (CT26) when combined with anti-PD-1 therapy (mDX400). It is a biologic (monoclonal antibody) associated with Merck.
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