Pharmacological RAS inhibition synergizes with CAR T cells for tumor killing (AACRPanCa 2026) - Oct 15, 2026 - Abstract #B104; "Hence, we sought to determine whether RAS inhibition could make PDAC tumors more responsive to CAR T cell therapy.Approach:Using xenograft and syngeneic mouse models of PDAC, we tested the impact of a RAS(ON) multi-selective inhibitor RMC-6236 and a KRAS G12D-selective inhibitor MRTX1133 on the anti-tumor activity of PDAC-targeting CAR T cells. In the presence of tumor-specific CAR T cells, pharmacologic RAS inhibition results in a STAT1-dependent increase in interferon signaling in PDAC cells, leading to increased sensitivity to CAR T cell cytotoxicity and improvements in anti-tumor efficacy in vivo. These studies provide a strong rationale for the clinical evaluation of RAS inhibitors in combination with engineered T cells.Citation Format:Jayne C. McDevitt, Feiyan Mo, Connor J. Hennessey, William B. Sullivan, Cynthia Clendenin, Il-Kyu Kim, Sydney M. Shaffer, Max M. Wattenberg, Robert H. Vonderheide, Carl H. June, Ben Z. Stanger. Pharmacological RAS inhibition..."
CAR T-Cell Therapy • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • MSLN
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Jayne C. McDevitt; Feiyan Mo; Connor J. Hennessey; William B. Sullivan; Cynthia Clendenin; Il-Kyu Kim; Sydney M. Shaffer; Max M. Wattenberg; Robert H. Vonderheide; Carl H. June; Ben Z. Stanger
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