Gutenberg Open Science: Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-10082

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DC Field	Value	Language
dc.contributor.author	Kropp, Korbinian N.	-
dc.contributor.author	Fatho, Martina	-
dc.contributor.author	Huduti, Enes	-
dc.contributor.author	Faust, Marilena	-
dc.contributor.author	Lübcke, Silke	-
dc.contributor.author	Lennerz, Volker	-
dc.contributor.author	Paschen, Annette	-
dc.contributor.author	Theobald, Matthias	-
dc.contributor.author	Wölfel, Thomas	-
dc.contributor.author	Wölfel, Catherine	-
dc.date.accessioned	2024-02-20T09:23:46Z	-
dc.date.available	2024-02-20T09:23:46Z	-
dc.date.issued	2023	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/10100	-
dc.description.abstract	Intorduction: Chondroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen, is expressed in melanoma but also other tumor entities and constitutes an attractive target for immunotherapeutic approaches. While recent preclinical reports focused on anti-CSPG4 chimeric antigen receptors (CAR), we here explore T-cell receptor (TCR)-based approaches targeting CSPG4. Methods: The TCRs of two CSPG4-reactive T-cell clones (11C/73 and 2C/165) restricted by the highly prevalent HLA-C07:01 allele were isolated and the respective αβTCR pairs were retrovirally expressed in CRISPR/Cas9-edited TCR-knockout T cells for functional testing. We also combined alpha and beta TCR chains derived from 11C/73 and 2C/165 in a cross-over fashion to assess for hemichain dominance. CSPG4+ melanoma, glioblastoma and lung cancer cell lines were identified and, if negative, retrovirally transduced with HLA-C07:01. Results: Functional tests confirmed specific recognition of CSPG4+HLA-C07:01+ target cells by the αβTCR retrieved from the parental T-cell clones and in part also by the cross-over TCR construct 2Cα-11Cβ. Despite high surface expression, the 11Cα-2Cβ combination, however, was not functional. Discussion: Collectively, 11C/73- and 2C/165-expressing T cells specifically and efficiently recognized CSPG4+HLA-C07:01+ cancer cells which warrants further preclinical and clinical evaluation of these TCRs.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-10082	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Frontiers in immunology	de
jgu.journal.volume	14	de
jgu.pages.alternative	1245559	de
jgu.publisher.year	2023	-
jgu.publisher.name	Frontiers Media	de
jgu.publisher.place	Lausanne	de
jgu.publisher.issn	1664-3224	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3389/fimmu.2023.1245559	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

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