RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 1323-1334 |
Number of pages | 12 |
Journal | Cancer Gene Therapy |
Volume | 31 |
Issue number | 9 |
Publication status | Published - Sept 2024 |
Peer-reviewed | Yes |
External IDs
PubMed | 38582787 |
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