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@ARTICLE{Immisch:274139,
author = {L. Immisch$^*$ and G. Papafotiou$^*$ and N. Gallarín
Delgado and V. Scheuplein and A. Paschen$^*$ and T.
Blankenstein and G. Willimsky$^*$},
title = {{T}argeting the recurrent {R}ac1{P}29{S} neoepitope in
melanoma with heterologous high-affinity {T} cell
receptors.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-00449},
pages = {1119498},
year = {2023},
abstract = {Recurrent neoepitopes are cancer-specific antigens common
among groups of patients and therefore ideal targets for
adoptive T cell therapy. The neoepitope FSGEYIPTV carries
the Rac1P29S amino acid change caused by a c.85C>T missense
mutation, which is the third most common hotspot mutation in
melanoma. Here, we isolated and characterized TCRs to target
this HLA-A*02:01-binding neoepitope by adoptive T cell
therapy. Peptide immunization elicited immune responses in
transgenic mice expressing a diverse human TCR repertoire
restricted to HLA-A*02:01, which enabled isolation of
high-affinity TCRs. TCR-transduced T cells induced
cytotoxicity against Rac1P29S expressing melanoma cells and
we observed regression of Rac1P29S expressing tumors in vivo
after adoptive T cell therapy (ATT). Here we found that a
TCR raised against a heterologous mutation with higher
peptide-MHC affinity (Rac2P29L) more efficiently targeted
the common melanoma mutation Rac1P29S. Overall, our study
provides evidence for the therapeutic potential of
Rac1P29S-specific TCR-transduced T cells and reveal a novel
strategy by generating more efficient TCRs by heterologous
peptides.},
keywords = {Rho (Rho GTPase) (Other) / TCR gene therapy (Other) /
humanized mouse models (Other) / melanoma (Other) /
neoantigen (Other)},
cin = {BE01 / ED01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331 / I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36875127},
pmc = {pmc:PMC9978334},
doi = {10.3389/fimmu.2023.1119498},
url = {https://inrepo02.dkfz.de/record/274139},
}