Reversed Targeting Module (RevTM)

The Reversed Targeting Module (RevTM) is a soluble, bispecific adaptor antibody that serves as the essential regulatory component of the RevCAR (Reversed Chimeric Antigen Receptor) platform, a switchable universal CAR-T cell system developed by GEMoaB and AvenCell Therapeutics (AvenCell, 2024; NIH, 2020). Unlike conventional CAR-T cells that directly recognize tumor antigens, RevCAR T-cells express a universal receptor that recognizes a specific, non-immunogenic peptide epitope, such as E5B9 or E7B6, derived from the human La/SS-B protein (NIH, 2020; MDPI, 2021). The RevTM molecule is engineered with dual specificity: one arm targets the peptide epitope on the RevCAR T-cell, while the other arm targets a specific tumor-associated antigen (TAA) on the cancer cell surface, such as CD123, CD33, or PSMA (NIH, 2020; MDPI, 2021). By cross-linking the T-cell to the tumor cell, the RevTM triggers T-cell activation, cytokine release, and targeted tumor lysis (NIH, 2020; AvenCell, 2024). This modular architecture allows for precise control over T-cell activity; the system can be switched off by stopping the administration of the RevTM, which has a short pharmacokinetic half-life of approximately 45-60 minutes, thereby mitigating potential toxicities like cytokine release syndrome (AvenCell, 2024; NIH, 2020). Additionally, the platform enables the targeting of multiple antigens or combinatorial AND-gate targeting to enhance specificity and overcome tumor escape mechanisms (NIH, 2020; MDPI, 2021).

Other names

RevTM adaptorTargeting ModuleRevCAR targeting moduleReversed adaptor antibodyR-TM

Bispecific binding that cross-links RevCAR-expressing T-cells (via a peptide epitope) to tumor cells (via a tumor-associated antigen), inducing T-cell activation and tumor cell killing.