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SITC 2022 | Combination myeloid cell and T-cell targeting as an effective anti-tumor strategy

Judith Varner, PhD, University of California, San Diego, CA, discusses the combination of myeloid cell and T-cell targeting as an effective anti-tumor strategy. PI3K is a myeloid cell-specific kinase that regulates the recruitment of myeloid cells into tumors. A small molecule inhibitor of PI3K kinase gamma has been shown to be an effective myeloid targeting agent that can boost the recruitment and activation of T-cells in tumors. PI3K gamma was also demonstrated to drive macrophage and myeloid cell mediated immune suppression. Thus, by inhibiting PI3K gamma, this allowed macrophages and other myeloid cells to become more proinflammatory, leading to tumor suppression. Notabley, combination therapy with checkpoint inhibitors and PI3K was demonstrated to completely eradicate certain tumors. Three Phase II clinical trials were carried out, exploring the small molecule inhibitor in triple negative breast cancer (TNBC) and urothelial cancer. The trial in urothelial cancer explored the PI3K gamma inhibitor in treatment resistant patients in the second line with nivolumab, demonstrating a double in overall-survival. In TNBC, an anti-PD-L1 combined with the PI3K gamma inhibitor eganelisib and nab-paclitaxel was investigated, demonstrating a strong enhancement of overall-survival and 90% tumor regression in both PD-L1-positive and negative patients. This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA.

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