Tumor-associated antigens recognized by Reverse T-cell Messenger (RevTM) adaptor molecules (RevTM-TAAs)

Tumor-associated antigens recognized by Reverse T-cell Messenger (RevTM) adaptor molecules represent the target landscape for a modular, switchable CAR-T cell platform known as UniCAR [1]. In this system, T-cells are engineered with a universal chimeric antigen receptor (UniCAR) that does not recognize tumor cells directly but instead binds to a specific peptide tag on a soluble adaptor molecule called a RevTM [1, 2]. These RevTM adaptors are bispecific, possessing a binding domain for the UniCAR-T cell and another for a specific tumor-associated antigen (TAA) such as CD123, PSMA, or CD33 [2, 3]. When the RevTM adaptor is administered, it bridges the UniCAR-T cell to the tumor cell, inducing T-cell activation, cytokine release, and redirected lysis of the target cell [1, 2]. This approach allows for the fine-tuning of T-cell activity through the dosing of the adaptor and provides a safety mechanism where the immune response can be rapidly halted by stopping the adaptor infusion [1, 4]. Clinical applications currently focus on hematologic malignancies like acute myeloid leukemia and solid tumors such as prostate cancer [4]. The system is designed to overcome the limitations of conventional CAR-T therapies, such as lack of control over T-cell activity and severe side effects [1]. By targeting specific TAAs through interchangeable adaptors, the platform offers a versatile and potentially safer alternative for treating various cancer types [2, 3].

Other names

UniCAR targeting modulesRevTM targetsSwitchable CAR-T antigensTargeting Modules (TM)

The RevTM adaptor molecules function as bispecific bridges that link universal CAR-T cells (UniCAR) to specific tumor-associated antigens, facilitating targeted tumor cell lysis only in the presence of the adaptor [1, 2].