Peptide Neo-Epitope-binding Chimeric Antigen Receptor (PNE-binding CAR) (PNE-binding CAR)

The Peptide Neo-Epitope-binding Chimeric Antigen Receptor (PNE-binding CAR) is a synthetic, extracellular receptor expressed on CLBR001 T cells, a switchable CAR-T cell therapy platform developed by Calibr at Scripps Research [1, 2]. Unlike conventional CAR-T cells that are engineered to recognize tumor antigens directly, the PNE-binding CAR domain is designed to bind with high specificity to a 14-amino acid peptide neo-epitope (PNE) derived from the yeast transcription factor GCN4 [1, 4]. This system functions through a bifunctional switch molecule, such as SWI019, which contains the PNE at one end and a tumor-targeting antibody fragment at the other [2, 3]. When the switch is administered, it bridges the CLBR001 T cell to the cancer cell, inducing CAR clustering and subsequent T cell activation, proliferation, and tumor lysis [1]. This modular approach allows for precise control over the timing and intensity of the immune response by adjusting the switch dosage, potentially improving the safety profile regarding cytokine release syndrome and neurotoxicity [2, 3]. Additionally, the platform is versatile, as the same CLBR001 T cells can be redirected to different tumor antigens by simply changing the switch molecule, facilitating the treatment of heterogeneous or evolving tumors [1, 2].

Other names

sCARswitchable CARGCN4-binding CARCLBR001 CAR52SR4-based CAR

The PNE-binding CAR domain binds to a peptide neo-epitope (PNE) on a bifunctional switch molecule, which simultaneously binds a tumor-associated antigen, creating an immunological synapse that triggers T cell cytotoxicity.