Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Targeting the recurrent Rac1P29S neoepitope in melanoma with heterologous high-affinity T cell receptors

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
[thumbnail of Supporting Information]
Preview
PDF (Supporting Information) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:Targeting the recurrent Rac1P29S neoepitope in melanoma with heterologous high-affinity T cell receptors
Creators Name:Immisch, L., Papafotiou, G., Gallarín Delgado, N., Scheuplein, V., Paschen, A., Blankenstein, T. and Willimsky, G.
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:Neoantigen, TCR Gene Therapy, Melanoma, Rho (Rho GTPase), Humanized Mouse Models, Animals, Mice
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA
Volume:14
Page Range:1119498
Date:16 February 2023
Official Publication:https://doi.org/10.3389/fimmu.2023.1119498
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library