In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 5, No. 7 ( 2019-07-05)
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 [ 18 F]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.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aaw5096
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2019
detail.hit.zdb_id:
2810933-8
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