Convertible chimeric antigen receptor (convertibleCAR)

The convertible chimeric antigen receptor (convertibleCAR) is a modular synthetic receptor platform designed to enhance the flexibility and safety of CAR-T cell therapies (Williams et al., 2020). It utilizes an engineered version of the human NKG2D receptor, which is modified to be inert to its natural ligands while maintaining high affinity for a specific, mutated version of the MICA ligand (Astellas Pharma, 2019). This system functions through the administration of "MicAbodies"—bispecific adapter molecules that bridge the convertibleCAR-T cell to a target tumor antigen (Sollid et al., 2020). This modularity allows clinicians to control the timing and intensity of the immune response by adjusting the dosage of the MicAbody, and it facilitates the targeting of multiple different antigens without the need to re-engineer the T-cells (Williams et al., 2020). Primarily investigated for the treatment of hematologic and solid malignancies, the convertibleCAR platform aims to mitigate common CAR-T risks such as cytokine release syndrome and antigen escape by providing a switchable and tunable mechanism of action (Astellas Pharma, 2019).

Other names

cCARNKG2D-based convertible CARModular chimeric antigen receptorUniversal CAR platform

The convertibleCAR system employs an engineered, inert NKG2D receptor on T-cells that is activated only when bridged to a tumor cell by a bispecific MicAbody adapter; this adapter binds simultaneously to the mutated NKG2D receptor and a specific tumor-associated antigen (Williams et al., 2020).