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Open AccessArticle

CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia

Department of Dermatology, Universtitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, 91052 Erlangen, Germany
*
Author to whom correspondence should be addressed.
The present work was performed in fulfillment of the requirements for obtaining the degree Dr. med. at the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU).
These authors contribute equally to this work.
Int. J. Mol. Sci. 2019, 20(11), 2764; https://doi.org/10.3390/ijms20112764
Received: 16 April 2019 / Revised: 24 May 2019 / Accepted: 27 May 2019 / Published: 5 June 2019
(This article belongs to the Special Issue CAR-T Cell Therapy)
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. View Full-Text
Keywords: CAR T cells; CSPG4; MLL-translocated leukemias; back-up target antigen; high-risk childhood B cell precursor leukemia CAR T cells; CSPG4; MLL-translocated leukemias; back-up target antigen; high-risk childhood B cell precursor leukemia
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MDPI and ACS Style

Harrer, D.C.; Schuler, G.; Dörrie, J.; Schaft, N. CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. Int. J. Mol. Sci. 2019, 20, 2764. https://doi.org/10.3390/ijms20112764

AMA Style

Harrer DC, Schuler G, Dörrie J, Schaft N. CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. International Journal of Molecular Sciences. 2019; 20(11):2764. https://doi.org/10.3390/ijms20112764

Chicago/Turabian Style

Harrer, Dennis C.; Schuler, Gerold; Dörrie, Jan; Schaft, Niels. 2019. "CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia" Int. J. Mol. Sci. 20, no. 11: 2764. https://doi.org/10.3390/ijms20112764

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