Indrani Das

Chimeric Antigen Receptor T-cell (CAR-T) therapy has had success in treating certain blood cancers but limited efficacy against solid tumors, largely due to poor tumor penetration. iRGD is a cyclic tumor-penetrating peptide that has been used to enhance delivery of chemo- and other cancer therapies. Here, we propose engineering of CAR-T cells that secrete iRGD (‘siRGD CAR-T’) as a novel solid tumor treatment strategy. We use patient samples to model and treat pancreatic cancer in vivo and hypothesize improved tumor infiltration and killing efficacy by siRGD CAR-T cells. Moreover, we expect that siRGD CAR-T therapy will contribute substantial remodeling of tumor microenvironment vasculature, stroma, and myeloid and lymphoid cell populations, and we will investigate these effects using spatial transcriptomics and single-cell RNA sequencing. Our findings will be imminently translatable to clinical trials for pancreatic cancer and preclinical studies for other cancer types.