Peptide Neo-Epitope-recognizing domain of CLBR001 (PNE-binding domain)

The PNE-recognizing domain on CLBR001 CAR-T cells is a specialized synthetic receptor designed for a switchable chimeric antigen receptor (sCAR-T) platform (Rodgers et al., 2016, PNAS). Unlike traditional CAR-T cells that directly target tumor antigens, CLBR001 cells express a receptor that specifically recognizes a small, non-immunogenic peptide neo-epitope (PNE), typically derived from the yeast transcription factor GCN4 (NCT04450069, ClinicalTrials.gov). This domain functions as the anchor point for a bifunctional switch molecule, such as SWI-019, which consists of the PNE linked to a targeting moiety like an anti-CD19 antibody fragment (Calibr, 2020). When the switch is administered, it bridges the CLBR001 CAR-T cell to the tumor cell, inducing T-cell activation, proliferation, and targeted cytotoxicity. This modular approach allows for precise control over the intensity and duration of the immune response by adjusting the dosage of the switch molecule, potentially mitigating common CAR-T toxicities like cytokine release syndrome. The system is currently being evaluated in clinical trials for B-cell malignancies.

Other names

PNE-binding scFvCLBR001 CAR receptorSwitchable CAR-T receptorGCN4-binding domain

The PNE-recognizing domain acts as a synthetic receptor that binds to a bifunctional switch molecule. This switch molecule bridges the CAR-T cell to a specific tumor antigen, triggering T-cell activation and tumor lysis only in the presence of the switch.