Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-10082
Authors: | Kropp, Korbinian N. Fatho, Martina Huduti, Enes Faust, Marilena Lübcke, Silke Lennerz, Volker Paschen, Annette Theobald, Matthias Wölfel, Thomas Wölfel, Catherine |
Title: | Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors |
Online publication date: | 20-Feb-2024 |
Year of first publication: | 2023 |
Language: | english |
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-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. Results: 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. Discussion: 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. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-10082 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Frontiers in immunology 14 |
Pages or article number: | 1245559 |
Publisher: | Frontiers Media |
Publisher place: | Lausanne |
Issue date: | 2023 |
ISSN: | 1664-3224 |
Publisher DOI: | 10.3389/fimmu.2023.1245559 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
---|---|---|---|---|---|
targeting_the_melanomaassocia-20240214143735778.pdf | 2.76 MB | Adobe PDF | View/Open |