CD137 (TNFRSF9, 4-1BB) agonist antibodies (mAb) have demonstrated potent anti-tumor activity with memory response while causing hepatotoxicity in mouse models. In clinical trials, the degrees of liver toxicity of anti-CD137 vary from grade 4 transaminitis (urelumab) to non-existent (utomilumab). To exploit the anti-tumor potential of CD137 signaling, we identified a new class of CD137 agonist mAbs with strong anti-tumor potency without significant transaminitis in vivo compared to CD137 agonists...
Thu Jan 23, 2020 17:17
Macrophages (M) play a critical role in tumor growth, immunosuppression and inhibition of adaptive immune responses in cancer. Hence, targeting signaling pathways in Ms that promote tumor immunosuppression will provide therapeutic benefit. PI3K has been recently established by our group and others as a novel immuno-oncology target. Herein, we report that a macrophage Syk-PI3K axis drives polarization of immunosuppressive Ms which establish an immunosuppressive tumor microenvironment in in vivo syngeneic...
Thu Jan 23, 2020 17:17
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