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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Haidy A. Saleh - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Nicola Mitwasi - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Liliana R. Loureiro - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Alexandra Kegler - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Karla Elizabeth González Soto - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Lydia Hoffmann - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Eugenia Crespo - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR), University Cancer Center (UCC) (Author)
  • Ralf Bergmann - , Semmelweis University (Author)
  • Michael Bachmann - , National Center for Tumor Diseases Dresden, University Cancer Centre Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK) Partner Site Dresden (Author)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR), National Center for Tumor Diseases (NCT) Dresden, German Cancer Research Center (DKFZ), University Cancer Center (UCC) (Author)

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

Original languageEnglish
Pages (from-to)1323-1334
Number of pages12
JournalCancer Gene Therapy
Volume31
Issue number9
Early online date6 Apr 2024
Publication statusPublished - Sept 2024
Peer-reviewedYes

External IDs

PubMed 38582787

Keywords