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Open AccessArticle

Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer

1
Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, 91054 Erlangen, Germany
2
Division of Genetics, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91058 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 696; https://doi.org/10.3390/cancers11050696
Received: 17 April 2019 / Revised: 8 May 2019 / Accepted: 16 May 2019 / Published: 20 May 2019
(This article belongs to the Special Issue Immunotherapy, Tumor Microenvironment and Survival Signaling)
Tumor cells can develop immune escape mechanisms to bypass T cell recognition, e.g., antigen loss or downregulation of the antigen presenting machinery, which represents a major challenge in adoptive T cell therapy. To counteract these mechanisms, we transferred not only one, but two receptors into the same T cell to generate T cells expressing two additional receptors (TETARs). We generated these TETARs by lentiviral transduction of a gp100-specific T cell receptor (TCR) and subsequent electroporation of mRNA encoding a second-generation CSPG4-specific chimeric antigen receptor (CAR). Following pilot experiments to optimize the combined DNA- and RNA-based receptor transfer, the functionality of TETARs was compared to T cells either transfected with the TCR only or the CAR only. After transfection, TETARs clearly expressed both introduced receptors on their cell surface. When stimulated with tumor cells expressing either one of the antigens or both, TETARs were able to secrete cytokines and showed cytotoxicity. The confirmation that two antigen-specific receptors can be functionally combined using two different methods to introduce each receptor into the same T cell opens new possibilities and opportunities in cancer immunotherapy. For further evaluation, the use of these TETARs in appropriate animal models will be the next step towards a potential clinical use in cancer patients. View Full-Text
Keywords: cancer; melanoma; immune escape; antigen loss; immunotherapy; chimeric antigen receptor; electroporation; lentivirus; lentiviral transduction cancer; melanoma; immune escape; antigen loss; immunotherapy; chimeric antigen receptor; electroporation; lentivirus; lentiviral transduction
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MDPI and ACS Style

Simon, B.; Harrer, D.C.; Schuler-Thurner, B.; Schuler, G.; Uslu, U. Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer. Cancers 2019, 11, 696. https://doi.org/10.3390/cancers11050696

AMA Style

Simon B, Harrer DC, Schuler-Thurner B, Schuler G, Uslu U. Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer. Cancers. 2019; 11(5):696. https://doi.org/10.3390/cancers11050696

Chicago/Turabian Style

Simon, Bianca; Harrer, Dennis C.; Schuler-Thurner, Beatrice; Schuler, Gerold; Uslu, Ugur. 2019. "Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer" Cancers 11, no. 5: 696. https://doi.org/10.3390/cancers11050696

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