Real time monitoring of CAR T-cells during leukemia treatment

Until the last two decades primary treatment options for cancer patients were surgery, chemotherapy, and radiation therapy. The FDA after years of clinical trials, in 2017 approved the use of the first two Chimeric Antigen Receptor (CAR) T-cell therapies Kymriah for lymphoblastic leukemia (ALL) and Yescarta for non-Hodgkin's lymphoma. CAR T-cell therapy, a form of immunotherapy utilizes a patient’s own T cells to recognize and kill tumors. Through a process of apheresis, a patient’s T cells that recognizes a protein called CD-19 are separated from the blood, genetically modified and then reintroduced into the patient’s circulatory system to directly attack and kill tumor cells. Response to CAR T-cell therapy is extremely rapid and effective, with 72% meaningful response to Yescarta within a month, of which 51% achieved complete remission. Despite their robust clinical efficiency, current clinical practice demands CAR T cell numbers to be serially assessed to monitor their occasioned lethal adverse effects. In this regard, a team of researchers from the Johns Hopkins Medical Institution led by Dr. Martin G.Pomper have designed a non-invasive serial PET scan imaging biomarker named CD19-tPSMA^(N9del) that can quantitatively probe CAR T cells’ target sites with high specificity in real time. They utilized urea-based reporter radiotracer composed of PSMA (prostate specific membrane antigen) and fluorine F-18 to tag CAR T cells to generate high signal-to-noise ratio at tumor and non-tumor sites that can be imaged using widely available clinical imaging devices such as PET scans. After 12 days of CD19-tPSMA^(N9del) labeled CAR T cells infusion into animal models, tumor shrinkage and elimination effects of the CAR T cells could be monitored in space and time at the primary tumor site. Interestingly, CAR T cells that infiltrated into metastatic bone marrow tumors could also be imaged, demonstrating the robustness of CD19-tPSMA^(N9del) in probing the heterogeneity of CAR T cell kinetics at both primary and metastatic tumor sites. The study also found similar numbers of CAR T cells in mouse tumors compared to that found in human biopsy specimens from the TRANSCEND trial, demonstrable of the translation potential of CD19-tPSMA^(N9del) as a radio tracer for CAR T cell leukemia therapy.