Jaspers JE, Khan JF, Godfrey WD, et al. IL-18-Secreting CAR T Cells Targeting DLL3 Are Highly Effective in Small Cell Lung Cancer Models. Journal of Clinical Investigation. 2023; (doi: 10.1172/JCI166028).
Delta-like protein 3 (DLL3) is a tumor-specific marker found on the cell surface of certain neuroendocrine cancers, making it a strong target candidate for chimeric antigen receptor (CAR) T cell therapy, according to new research. Researchers engineered a CAR targeting DLL3 and tested it in xenograft and murine models of small cell lung cancer (SCLC). The approach achieved antitumor efficacy, which was amplified when the CAR T cell was designed to produce interleukin-18 (IL-18). Secretion of the proinflammatory cytokine in a murine metastatic SCLC model boosted activation of CAR T cells and tumor-infiltrating lymphocytes while increasing infiltration, repolarization, and activation of antigen-expressing cells. Investigators believe additional beneficial effects from human IL-18-producing anti-DLL3 CAR T cells — greater memory phenotype, reduced exhaustion, and induced durable responses — can be enhanced even more with anti-PD-1 suppression.
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