Development of an in situ CAR-T cell protocol through optical and PSMA-targeted PET imaging. (PubMed, Proc Natl Acad Sci U S A)
Herein, we develop an approach for in situ T cell generation, tracking, and functional assessment using anti-CD5-conjugated lipid nanoparticles for codelivering CD19 CAR mRNA (mCAR19) and a prostate-specific membrane antigen mRNA (mPSMA) tag. With interleukin-7 (IL-7) preconditioning and repeated administration, this approach achieves tumor-free survival in 75% of B cell lymphoma-bearing mice (similar efficacy to ex vivo approaches), and through PET imaging of 68Ga-PSMA-617, the generation and tumor infiltration of in situ-engineered PSMA-tagged CD19 CAR-T cells is validated.