CLBR001 Chimeric Antigen Receptor (CLBR001 CAR)

CLBR001 is a switchable chimeric antigen receptor (sCAR) expressed on autologous T cells, representing a modular approach to cellular immunotherapy (Calibr at Scripps Research). Unlike traditional CAR-T cells that directly recognize tumor antigens, the extracellular binding domain of the CLBR001 CAR is engineered to bind a specific 14-amino acid peptide neo-epitope (PNE) derived from the yeast transcription factor GCN4 (Rodgers et al., 2016, PNAS). This CAR-T cell remains inactive until a bifunctional switch molecule, such as SWI019, is administered to bridge the CAR-T cell to a specific tumor antigen like CD19 (ClinicalTrials.gov, NCT04450069). This design allows for the control of T cell activity, kinetics, and specificity by adjusting the dosage or type of the switch molecule, potentially reducing the risk of severe toxicities like cytokine release syndrome (Calibr at Scripps Research). CLBR001 is currently being evaluated in clinical trials for patients with relapsed or refractory B-cell malignancies, where it aims to provide a safer and more versatile alternative to conventional CAR-T therapies (ASCO, 2023).

Other names

sCARSwitchable CARPNE-binding CARGCN4-binding CARCLBR001 CAR-T52SR4 scFv

The extracellular binding domain of the CLBR001 CAR specifically recognizes and binds to a peptide neo-epitope (PNE) tag present on a bifunctional switch molecule. This binding, in conjunction with the switch molecule's binding to a tumor-associated antigen, facilitates the formation of a synthetic immunological synapse, leading to the phosphorylation of intracellular signaling domains (CD3-zeta and 4-1BB) and subsequent T cell activation, proliferation, and cytotoxic activity against the target cell.