Peptide neo-epitope-binding chimeric antigen receptor (sCAR)

The CLBR001 switchable CAR extracellular domain is a synthetic receptor component of the CLBR001 autologous T-cell therapy platform developed by Calibr at Scripps Research [1]. This extracellular domain (ECD) is engineered as a single-chain variable fragment (scFv) that specifically recognizes a 14-amino acid peptide neo-epitope (PNE) derived from the yeast transcription factor GCN4, rather than a native tumor antigen [2]. The CLBR001 CAR-T cells remain in an off state until a bifunctional switch molecule, such as SWI019, is administered to the patient [3]. The switch molecule serves as a bridge, binding the CAR ECD via the PNE tag and simultaneously binding a tumor-associated antigen, such as CD19, on the surface of malignant cells [2][4]. This interaction facilitates the formation of an immunological synapse, triggering intracellular signaling through CD3-zeta and 4-1BB domains to induce T-cell proliferation and cytotoxic activity [1][2]. This modular design allows for precise control over the timing and intensity of the immune response, providing a mechanism to mitigate toxicities like cytokine release syndrome (CRS) by adjusting the switch dosage [3][5]. Furthermore, the platform enables the potential to target multiple different antigens using a single CAR-T cell product by employing various antigen-specific switches [1][4].

Other names

sCARPNE-binding CARGCN4-binding CARSwitchable chimeric antigen receptorCLBR001 CAR52SR4 scFv-based CAR

The extracellular domain binds a peptide neo-epitope (PNE) on a bifunctional switch molecule, which simultaneously binds a tumor-associated antigen, creating a bridge that triggers T-cell receptor signaling and cytotoxic activity.