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AO-176 + pembrolizumab is a combination therapy under clinical investigation for the treatment of select solid tumors, including relapsed, platinum-resistant ovarian cancer, endometrial cancer, and gastroesophageal cancer. AO-176 is a humanized IgG2 monoclonal antibody that targets CD47, an innate immune checkpoint protein often overexpressed on tumor cells. By blocking the "don't eat me" signal mediated by CD47-SIRPα interaction, AO-176 promotes phagocytosis of tumor cells by macrophages. It also directly kills tumor cells and induces immunogenic cell death via DAMPs (Damage Associated Molecular Patterns). Notably, it binds preferentially to tumor cells—especially in acidic microenvironments—over normal tissues[1][5][8]. Pembrolizumab (Keytruda) is a humanized monoclonal antibody targeting PD‑1 on T lymphocytes; it blocks PD‑1/PD-L1 interactions to enhance T-cell-mediated anti-tumor immunity[6]. The rationale for combining these agents lies in their complementary mechanisms: simultaneous blockade of innate (CD47) and adaptive (PD‑1) immune checkpoints may produce synergistic anti-tumor effects[1][5].
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