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@ARTICLE{Kropp:284800,
author = {K. N. Kropp$^*$ and M. Fatho$^*$ and E. Huduti$^*$ and M.
Faust$^*$ and S. Lübcke$^*$ and V. Lennerz$^*$ and A.
Paschen$^*$ and M. Theobald$^*$ and T. Wölfel$^*$ and C.
Wölfel$^*$},
title = {{T}argeting the melanoma-associated antigen {CSPG}4 with
{HLA}-{C}*07:01-restricted {T}-cell receptors.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-02103},
pages = {1245559},
year = {2023},
abstract = {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.},
keywords = {CSPG4 (Other) / T cell receptor (TCR) (Other) / TCR
hemichain dominance (Other) / chondroitin sulfate
proteoglycan 4 (Other) / tumor immunotherapy (Other)},
cin = {FM01 / ED01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331 / I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37849763},
pmc = {pmc:PMC10577170},
doi = {10.3389/fimmu.2023.1245559},
url = {https://inrepo02.dkfz.de/record/284800},
}