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

Sci Adv. 2024 Sep 20;10(38):eadn3816. doi: 10.1126/sciadv.adn3816. Epub 2024 Sep 18.

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.

MeSH terms

  • Animals
  • Antigens / immunology
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Mice
  • Positron-Emission Tomography / methods
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / immunology
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

  • Receptors, Chimeric Antigen
  • Antigens