1. Imaging CAR T cell therapy with PSMA-targeted positron emission tomography
- Author
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Polina Sysa-Shah, Jon Jones, Steven P. Rowe, Yong Du, Andrew Park, Mary Brummet, Tamara M. Chinn, David Jeffrey Huss, Hye Hyun Ahn, Il Minn, Martin G. Pomper, and Hyam I. Levitsky
- Subjects
Glutamate Carboxypeptidase II ,medicine.medical_treatment ,T cell ,T-Lymphocytes ,Antigens, CD19 ,Receptors, Antigen, T-Cell ,Immunotherapy, Adoptive ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Urea ,Receptor ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Leukemia, Experimental ,medicine.diagnostic_test ,business.industry ,Lysine ,Immunotherapy ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Chimeric antigen receptor ,3. Good health ,Leukemia ,medicine.anatomical_structure ,Positron emission tomography ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Research Highlights ,Antigens, Surface ,Cancer research ,Bone marrow ,business - Abstract
Chimeric antigen receptor (CAR) T cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional T cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Non-invasive, serial imaging of CAR T cell therapy using a reporter transgene can address those issues quantitatively. We have transduced anti-CD19 CAR T cells with the prostate-specific membrane antigen (PSMA) because it is a human protein with restricted normal tissue expression and has an expanding array of positron emission tomography (PET) and therapeutic radioligands. We demonstrate that CD19-tPSMA(N9del) CAR T cells can be tracked with [18F]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia. Divergence between the number of CD19-tPSMA(N9del) CAR T cells in peripheral blood and bone marrow and those in tumor was evident. These findings underscore the need for non-invasive repeatable monitoring of CAR T cell disposition clinically.
- Published
- 2018