Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool
Julia Fröse, Jennifer E. Rowley, Ali Salehi Farid, Taha Rakhshandehroo, P Leclerc, Howard H. Mak, Harris H. Allen, Heydar Moravej, Leila Munaretto, Luis R. Millán-Barea, Elisabeth Codet, Hannah Jorinde Glöckner, Caron A. Jacobson, Michael T. Hemann, Mohammad Rashidian
Abstract
CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy. Positron emission tomography (PET) offers a comprehensive view of CAR T cell homing, especially in critical organs such as lymphoid structures and bone marrow. This information will help assess treatment response and predict relapse risk. Current PET imaging methods for CAR T require genetic modifications, limiting clinical use. To overcome this, we developed an antigen-based imaging approach enabling whole-body CAR T cell imaging. The probe detects CAR T cells in vivo without affecting their function. In an immunocompetent B cell leukemia model, CAR-PET signal in the spleen predicted early mortality risk. The antigen-based CAR-PET approach allows assessment of CAR T therapy responses without altering established clinical protocols. It seamlessly integrates with FDA-approved and future CAR T cell generations, facilitating broader clinical application.