CliniMACS Prodigy Manufacturing of Switchable, AND-Gate CAR T Cells

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragen

Beitragende

Abstract

The Reverse Chimeric Antigen Receptor (RevCAR) system is an adapter CAR T cell technology that allows the precise tuning of T cell activity and, thus, improved safety management. RevCAR T cells recognize and eradicate tumor cells via a bispecific adapter molecule, termed the RevCAR Target Module (RevTM). To further reduce the risk of on-target off-tumor toxicities, Dual-RevCAR T cells can be employed. These cells harbor two different RevCAR constructs, with the signaling domain of either CD3zeta or CD28. Therefore, Dual-RevCAR T cells only exert their full function when both RevCAR constructs are triggered simultaneously upon recognition of two different tumor antigens via RevTMs, enabling a precise AND-gate targeting approach and rendering them highly interesting for clinical application. For this purpose, standardized and reproducible clinical-grade cell manufacturing is required, for which the CliniMACS Prodigy can be used. Here, we present that automated processing of RevCAR and Dual-RevCAR T cells via the CliniMACS Prodigy results in potent expansion, strong transduction, and a favorable phenotype for clinical application. Moreover, obtained cell products were highly functional in a strict RevTM-dependent manner for both monospecific and AND-gate targeting, clearly underlining their high potential for clinical application against various tumor entities.

Details

OriginalspracheEnglisch
FachzeitschriftInternational journal of molecular sciences
Jahrgang26
Ausgabenummer11
PublikationsstatusVeröffentlicht - 23 Mai 2025
Peer-Review-StatusNein

Externe IDs

PubMedCentral PMC12154027
Scopus 105007726463

Schlagworte

Schlagwörter

  • Humans, Receptors, Chimeric Antigen/immunology, Immunotherapy, Adoptive/methods, T-Lymphocytes/immunology, CD28 Antigens/immunology, CD3 Complex/immunology, Neoplasms/therapy, Receptors, Antigen, T-Cell/genetics, Antigens, Neoplasm/immunology