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Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T
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Nanobody Based Dual Specific CARs

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium
Center for Molecular Medicine Cologne (CMMC) and Departement of Internal Medicine, University of Cologne, 50923 Cologne, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 403;
Received: 27 December 2017 / Revised: 22 January 2018 / Accepted: 24 January 2018 / Published: 30 January 2018
(This article belongs to the Special Issue Chimeric Antigen Receptor (CAR) T Cell Therapy)
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Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity. View Full-Text
Keywords: CAR T cell; nanobody; antigen escape CAR T cell; nanobody; antigen escape

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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De Munter, S.; Ingels, J.; Goetgeluk, G.; Bonte, S.; Pille, M.; Weening, K.; Kerre, T.; Abken, H.; Vandekerckhove, B. Nanobody Based Dual Specific CARs. Int. J. Mol. Sci. 2018, 19, 403.

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