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AO-176 + paclitaxel is a combination therapy under clinical investigation for cancer treatment. AO-176 is a next-generation, humanized IgG2 monoclonal antibody that targets CD47, an innate immune checkpoint receptor overexpressed on many tumor cells. By blocking the interaction between CD47 and signal regulatory protein alpha (SIRPα) on phagocytes, AO-176 disrupts the "don't eat me" signal that allows tumors to evade immune clearance. Its mechanisms include promoting phagocytosis of tumor cells, inducing direct programmed cell death (type III), and triggering immunogenic cell death with preferential binding to tumor cells over normal cells and enhanced activity in acidic tumor microenvironments. Paclitaxel is a well-established chemotherapeutic agent that stabilizes microtubules by promoting their assembly and preventing depolymerization, thereby inhibiting mitosis and inducing apoptosis in rapidly dividing cancer cells. The combination of AO-176 with paclitaxel aims to enhance antitumor efficacy through complementary mechanisms—immune-mediated clearance by AO-176 and cytotoxicity via microtubule stabilization by paclitaxel[1][3][4][5][6].
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