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A combination investigational immunotherapy regimen consisting of three monoclonal antibodies: **AGEN1571**, **balstilimab** (anti–PD-1), and **botensilimab** (Fc-enhanced anti–CTLA-4). Botensilimab is engineered to provide broad immune activation by enhancing innate and adaptive anti-tumor responses, overcoming the limitations of first-generation CTLA-4 inhibitors by engaging activating Fc receptors, depleting regulatory T cells, activating myeloid cells, and inducing immune memory. Balstilimab targets the PD-1 pathway to sustain T-cell–mediated anti-tumor responses. AGEN1571 is a monoclonal antibody primarily targeting the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) checkpoint; intended to reverse tumor immune escape and synergize with checkpoint blockade, though its role in combination with botensilimab and balstilimab remains investigational. This triple therapy is under clinical investigation, primarily by Agenus, for **microsatellite-stable (MSS) metastatic colorectal cancer** and other refractory solid tumors, aiming to enhance response in tumors typically resistant to standard immunotherapies[1][2][5][9].
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