Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool

• DOI: 10.1126/sciadv.adn3816
• Publication Date: 2024-09-18T17:59:11Z
• Authors: Julia Fröse; Jennifer Rowley; Ali Salehi Farid; Taha Rakhshandehroo; Paul Leclerc; Howard Mak; Harris Allen; Heydar Moravej; Leila Munaretto; Luis Millan-Barea; Elisabeth Codet; Hannah Glockner; Caron Jacobson; Michael Hemann; Mohammad Rashidian
• Keywords: Mice; Receptors, Chimeric Antigen; T-Lymphocytes; Positron-Emission Tomography; Animals; Humans; Biomedicine and Life Sciences; Antigens; Immunotherapy, Adoptive

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.