Dual RevCAR T-cells

Dual RevCAR T-cells are an investigational adapter-based chimeric antigen receptor (CAR) T-cell therapy designed with an "AND-gate" logic system to improve the precision and safety of targeting solid tumors. Developed by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), this platform involves T cells engineered to express two separate, non-functional RevCARs: a signaling (SIG) RevCAR containing the CD3ζ domain and a co-stimulatory (COS) RevCAR containing the CD28 domain. These receptors do not recognize tumor antigens directly; instead, they bind to specific peptide epitopes (E7B6 and E5B9) on bispecific adapter molecules known as RevCAR Target Modules (RevTMs). Full T-cell activation and subsequent tumor lysis occur only when both the SIG and COS RevCARs are simultaneously engaged by their respective RevTMs on a target cell expressing both corresponding tumor-associated antigens (TAAs). This combinatorial approach is intended to spare healthy tissues that may express only one of the targeted antigens, thereby reducing off-tumor toxicity. The system has been explored for various indications, including glioblastoma, colorectal cancer, and prostate cancer, using targets such as EGFR, GD2, CEA, EpCAM, PSCA, and PD-L1.

Other names

Dual-RevCAR T cells