Tumor-associated antigens recognized by RevTMs

Tumor-associated antigens recognized by RevTMs represent a diverse class of cell-surface molecules targeted by the Reverse Target Module (RevTM) platform, a component of the switchable RevCAR T-cell system developed by AvenCell (formerly GEMoaB) [haematologica.org, https://www.haematologica.org; frontiersin.org, https://www.frontiersin.org]. Unlike conventional CAR-T therapies where the receptor directly binds a tumor antigen, RevCAR T-cells express a "Reverse" receptor that displays a peptide epitope, such as E5B9 or E7B6, making the T-cells inherently inert [ashpublications.org, https://ashpublications.org; hzdr.de, https://www.hzdr.de]. The RevTM serves as a bispecific adapter molecule that bridges the RevCAR T-cell and the tumor cell by simultaneously binding the CAR's peptide epitope and a specific tumor-associated antigen (TAA) [nih.gov, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221436/]. This modular design provides a safety "on/off" switch, as T-cell activation is strictly dependent on the presence and dosage of the short-lived RevTM adapter [diva-portal.org, https://www.diva-portal.org]. Key antigens targeted by this platform include CD123 and CD33 for acute myeloid leukemia, PSMA for prostate cancer, and EGFR, GD2, CEA, and EpCAM for various solid tumors [mdpi.com, https://www.mdpi.com/2072-6694/13/19/4785]. Additionally, the platform is being adapted to target autoreactive B-cells in autoimmune conditions like immune thrombotic thrombocytopenic purpura (iTTP) by recognizing antigens such as CD19 or the anti-ADAMTS13 B-cell receptor [haematologica.org, https://www.haematologica.org]. By allowing for gated targeting (e.g., AND-gate logic) and rapid termination of activity, the RevTM system aims to mitigate common CAR-T risks such as cytokine release syndrome and on-target off-tumor toxicity [hzdr.de, https://www.hzdr.de].

Other names

RevTM targetsReverse Target Module antigensRevCAR-targeted antigensTAAs recognized by RevTMs

Redirection of RevCAR-expressing T-cells to tumor-associated antigens via bispecific adapter molecules (RevTMs) that bridge the T-cell and the target cell.