Direkt zum Inhalt

Harrer, Dennis Christoph ; Schlierkamp-Voosen, Tim ; Barden, Markus ; Pan, Hong ; Xydia, Maria ; Herr, Wolfgang ; Dörrie, Jan ; Schaft, Niels ; Abken, Hinrich

Chimeric Antigen Receptor (CAR) T Cells Releasing Soluble SLAMF6 Isoform 2 Gain Superior Anti-Cancer Cell Functionality in an Auto-Stimulatory Fashion

Harrer, Dennis Christoph , Schlierkamp-Voosen, Tim, Barden, Markus, Pan, Hong, Xydia, Maria, Herr, Wolfgang, Dörrie, Jan, Schaft, Niels und Abken, Hinrich (2025) Chimeric Antigen Receptor (CAR) T Cells Releasing Soluble SLAMF6 Isoform 2 Gain Superior Anti-Cancer Cell Functionality in an Auto-Stimulatory Fashion. Cells 14 (12), S. 901.

Veröffentlichungsdatum dieses Volltextes: 02 Jul 2025 16:24
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.77038


Zusammenfassung

T cells equipped with chimeric antigen receptors (CARs) have evolved into an essential pillar of lymphoma therapy, reaching second-line treatment. In solid cancers, however, a dearth of lasting CAR T cell activation poses the major obstacle to achieving a substantial and durable anti-tumor response. To extend T cell cytotoxic capacities, we engineered CAR T cells to constitutively release an ...

T cells equipped with chimeric antigen receptors (CARs) have evolved into an essential pillar of lymphoma therapy, reaching second-line treatment. In solid cancers, however, a dearth of lasting CAR T cell activation poses the major obstacle to achieving a substantial and durable anti-tumor response. To extend T cell cytotoxic capacities, we engineered CAR T cells to constitutively release an immunostimulatory variant of soluble SLAMF6. While wild-type SLAMF6 induces T cell exhaustion, CAR T cells with the soluble Δ17-65 SLAMF6 variant exhibited refined, CAR redirected functionality compared to canonical CAR T cells. CD28-ζ CAR T cells releasing soluble SLAMF6 increased IFN-γ secretion and augmented CD25 upregulation on CD4+ CAR T cells upon CAR engagement by pancreatic carcinoma and melanoma cells. Moreover, under conditions of repetitive antigen encounter, SLAMF6-secreting CAR T cells evinced superior cytotoxic capacity in the long term. Mechanistically, SLAMF6-secreting CAR T cells showed predominantly a central memory phenotype, a PD-1- TIGIT- double negative profile, and reduced expression of exhaustion-related transcription factors IRF-4 and TOX with augmented amplification and persistence capacities. Overall, CAR T cells engineered with the release isoform 2 SLAMF6 establish an auto-stimulatory loop with the potential to boost the cytolytic attack against solid tumors.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftCells
Verlag:MDPI
Band:14
Nummer des Zeitschriftenheftes oder des Kapitels:12
Seitenbereich:S. 901
Datum14 Juni 2025
InstitutionenMedizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Projekte
Gefördert von: Deutsche Forschungsgemeinschaft (DFG) (324392634)
Identifikationsnummer
WertTyp
10.3390/cells14120901DOI
Stichwörter / KeywordsCAR T cell; adoptive T cell therapy; checkpoint; stimulation; exhaustion
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-770385
Dokumenten-ID77038

Bibliographische Daten exportieren

Nur für Besitzer und Autoren: Kontrollseite des Eintrags

nach oben