RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 1323-1334 |
| Seitenumfang | 12 |
| Fachzeitschrift | Cancer Gene Therapy |
| Jahrgang | 31 |
| Ausgabenummer | 9 |
| Frühes Online-Datum | 6 Apr. 2024 |
| Publikationsstatus | Veröffentlicht - Sept. 2024 |
| Peer-Review-Status | Ja |
Externe IDs
| PubMed | 38582787 |
|---|