RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Haidy A. Saleh - , Helmholtz-Zentrum Dresden-Rossendorf, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Nicola Mitwasi - , Helmholtz-Zentrum Dresden-Rossendorf, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Liliana R. Loureiro - , Helmholtz-Zentrum Dresden-Rossendorf, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Alexandra Kegler - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Karla Elizabeth González Soto - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Lydia Hoffmann - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Eugenia Crespo - , Universitäts KrebsCentrum Dresden, Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf, Medizinische Fakultät Carl Gustav Carus Dresden, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Ralf Bergmann - , Semmelweis University (Autor:in)
  • Michael Bachmann - , Institut für Immunologie, Nationales Centrum für Tumorerkrankungen Dresden, Deutsches Krebsforschungszentrum, DKFZ Standort Dresden, Universitäts KrebsCentrum Dresden, Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf, Nationales Zentrum für Tumorerkrankungen (NCT) Dresden, Deutsches Krebsforschungszentrum (DKFZ), Universitäts KrebsCentrum Dresden (UCC) (Autor:in)

Abstract

In recent studies, we have established the unique adapter chimeric antigen receptor (CAR) platform RevCAR which uses, as an extracellular CAR domain, a peptide epitope instead of an antibody domain. RevCAR adapters (termed RevCAR target modules, RevTMs) are bispecific antibodies that enable the reversible ON/OFF switch of the RevCAR system, improving the safety compared to conventional CARs. Here, we describe for the first time its use for retargeting of both T and NK-92 cells. In addition, we describe the development and preclinical validation of a novel RevTM for targeting of the fibroblast growth factor-inducible 14 (Fn14) surface receptor which is overexpressed on Glioblastoma (GBM) cells, and therefore serves as a promising target for the treatment of GBM. The novel RevTM efficiently redirects RevCAR modified T and NK-92 cells and leads to the killing of GBM cells both in vitro and in vivo. Tumor cell killing is associated with increased IL-2, TNF-α and/or IFN-γ secretion. Hence, these findings give an insight into the complementary potential of both RevCAR T and NK-92 systems as a safe and specific immunotherapeutic approach against GBM.

Details

OriginalspracheEnglisch
Seiten (von - bis)1323-1334
Seitenumfang12
FachzeitschriftCancer Gene Therapy
Jahrgang31
Ausgabenummer9
PublikationsstatusVeröffentlicht - Sept. 2024
Peer-Review-StatusJa

Externe IDs

PubMed 38582787

Schlagworte