Imaging CAR T cell therapy with PSMA-targeted positron emission tomography
| Autor: | 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, Hyam I. Levitsky |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Radiol Imaging Cancer |
| ISSN: | 2375-2548 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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