Harrer DC, Schuler G, Dörrie J, Schaft N (2019)
Publication Type: Journal article
Publication year: 2019
Book Volume: 20
Journal Issue: 11
DOI: 10.3390/ijms20112764
The advent of CD19-specific chimeric antigen receptor (CAR) T cells has proven to be a powerful asset in the arsenal of cancer immunotherapy of acute lymphoblastic leukemia and certain B cell lymphomas. However, a sizable portion of patients treated with CD19-CAR T cells relapse with CD19-negative cancer cells, necessitating the quest for back-up antigens. Chondroitin sulfate proteoglycan 4 (CSPG4) expression has been reported on leukemic blasts bearing the ill-fated MLL 11q23 rearrangement. We aimed at exploring the use of CSPG4-specific CAR T cells against mixed-lineage leukemia (MLL)-rearranged leukemic blasts, using the precursor B cell leukemia cell line KOPN8 (MLL-MLLT1 translocation) as a model. First, we confirmed CSPG4 expression on KOPN8 cells. Bulk T cells electroporated with mRNA encoding a CSPG4-specific CAR upregulated activation markers and secreted the Th1 cytokines TNF and IFNγ in an antigen-specific manner upon co-culture with KOPN8 cells. More importantly, CSPG4-specific CAR T cells evinced specific degranulation towards KOPN8 cells and specifically lysed KOPN8 target cells in chromium lysis experiments. CSPG4 is a well-established CAR target in cutaneous melanoma. Here, we provide proof-of-principle data for the use of CSPG4-specific CAR T cells against MLL-translocated leukemias.
APA:
Harrer, D.C., Schuler, G., Dörrie, J., & Schaft, N. (2019). CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. International Journal of Molecular Sciences, 20(11). https://doi.org/10.3390/ijms20112764
MLA:
Harrer, Dennis C., et al. "CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia." International Journal of Molecular Sciences 20.11 (2019).
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