Development of an in situ CAR-T cell protocol through optical and PSMA-targeted PET imaging
Abstract
In situ T cell transfection methods overcome the complexity and high costs associated with conventional chimeric antigen receptor (CAR)-T therapy. However, the in situ CAR-T cell approach operates within the patient’s complex immune environment and bypasses preinfusion ex vivo cellular quality controls, necessitating advanced imaging techniques to track immune cell migration and function. Positron emission tomography (PET) can detect biochemical processes in patients and, when combined with a radiotracer specific for the engineered cells, can monitor CAR-T cell trafficking. 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 68 Ga-PSMA-617, the generation and tumor infiltration of in situ-engineered PSMA-tagged CD19 CAR-T cells is validated.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Nisi Zhang
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Jai Woong Seo
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Elise Robinson
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Angelie Rivera-Rodriguez
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
James Wang
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Yutong Guo
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Debra K. Czerwinski
Division of Oncology, Department of Medicine, Stanford Cancer Institute
Ha Rin Kim
Division of Oncology, Department of Medicine, Stanford University School of Medicine
Spencer K. Tumbale
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Marina N. Raie
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Basit L. Jan
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Gokce Engudar
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Adrienne Sallets
Division of Oncology, Department of Medicine, Stanford Cancer Institute
Il Minn
Department of Radiology, University of Texas Southwestern Medical Center
Martin G. Pomper
Department of Radiology, University of Texas Southwestern Medical Center
Ronald Levy
Division of Oncology, Department of Medicine, Stanford Cancer Institute
Katherine W. Ferrara
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University