%0 Journal Article
%A Kropp, Korbinian N
%A Fatho, Martina
%A Huduti, Enes
%A Faust, Marilena
%A Lübcke, Silke
%A Lennerz, Volker
%A Paschen, Annette
%A Theobald, Matthias
%A Wölfel, Thomas
%A Wölfel, Catherine
%T Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors.
%J Frontiers in immunology
%V 14
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2023-02103
%P 1245559
%D 2023
%X 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.The TCRs of two CSPG4-reactive T-cell clones (11C/73 and 2C/165) restricted by the highly prevalent HLA-C*07:01 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-C*07:01.Functional tests confirmed specific recognition of CSPG4+HLA-C*07:01+ 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.Collectively, 11C/73- and 2C/165-expressing T cells specifically and efficiently recognized CSPG4+HLA-C*07:01+ cancer cells which warrants further preclinical and clinical evaluation of these TCRs.
%K CSPG4 (Other)
%K T cell receptor (TCR) (Other)
%K TCR hemichain dominance (Other)
%K chondroitin sulfate proteoglycan 4 (Other)
%K tumor immunotherapy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37849763
%2 pmc:PMC10577170
%R 10.3389/fimmu.2023.1245559
%U https://inrepo02.dkfz.de/record/284800