Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Abstract
- <jats:sec><jats:title>Intorduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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<jats:sup>+</jats:sup> melanoma, glioblastoma and lung cancer cell lines were identified and, if negative, retrovirally transduced with HLA-C*07:01.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Functional tests confirmed specific recognition of CSPG4<jats:sup>+</jats:sup>HLA-C*07:01<jats:sup>+</jats:sup> 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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Collectively, 11C/73- and 2C/165-expressing T cells specifically and efficiently recognized CSPG4<jats:sup>+</jats:sup>HLA-C*07:01<jats:sup>+</jats:sup> cancer cells which warrants further preclinical and clinical evaluation of these TCRs.</jats:p></jats:sec>
- Autoren
- Korbinian N Kropp
- Martina Fatho
- Enes Huduti
- Marilena Faust
- Silke Lübcke
- Volker Lennerz
- Annette Paschen
- Matthias Theobald
- Thomas Wölfel
- Catherine Wölfel
- DOI
- 10.3389/fimmu.2023.1245559
- eISSN
- 1664-3224
- Zeitschrift
- Frontiers in Immunology
- Online publication date
- 2023
- Status
- Published online
- Herausgeber
- Frontiers Media SA
- Herausgeber URL
- http://dx.doi.org/10.3389/fimmu.2023.1245559
- Datum der Datenerfassung
- 2023
- Titel
- Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors
- Ausgabe der Zeitschrift
- 14
Datenquelle: Crossref
- Andere Metadatenquellen:
-
- Author's licence
- CC-BY
- Autoren
- Korbinian N Kropp
- Martina Fatho
- Enes Huduti
- Marilena Faust
- Silke Lübcke
- Volker Lennerz
- Annette Paschen
- Matthias Theobald
- Thomas Wölfel
- Catherine Wölfel
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- DFG-491381577-G
- Resource version
- Published version
- DOI
- 10.3389/fimmu.2023.1245559
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 1664-3224
- Zeitschrift
- Frontiers in immunology
- Schlüsselwörter
- 610 Medizin
- 610 Medical sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 1245559
- Datum der Veröffentlichung
- 2023
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/10100
- Herausgeber
- Frontiers Media
- Datum der Datenerfassung
- 2024
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2024
- Zugang
- Public
- Titel
- Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors
- Ausgabe der Zeitschrift
- 14
Files
targeting_the_melanomaassocia-20240214143735778.pdf
Datenquelle: OPENSCIENCE.UB