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

Menée à l'aide de lignées cellulaires et de modèles murins, cette étude met en évidence l'intérêt d'une sonde marquée au zirconium 89 Zr et ciblant l'antigène CD19 pour détecter en temps réel des lymphocytes CAR-T et évaluer leur efficacité thérapeutique à l'aide de la tomographie par émission de positrons

Résumé en anglais

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. Antigen-based CAR-PET imaging detects CD19 CAR T cells with clarity, offering insights into the efficacy of CAR-T therapy.