Peptide neo-epitope (PNE) (PNE)

The Linker-Label-Epitope neo-epitope, frequently referred to as a Peptide Neo-Epitope (PNE), is a synthetic target used in switchable chimeric antigen receptor (sCAR-T) cell therapies to provide tunable control over T-cell activity (Rodgers et al., 2016, PNAS). Unlike standard CAR-T therapies that target endogenous proteins, sCAR-T cells are engineered to recognize this specific, non-natural peptide sequence or label (Ma et al., 2016, PNAS). The PNE is incorporated into a bifunctional adapter molecule (or switch) that also contains a targeting domain, such as a Fab fragment, specific for a tumor-associated antigen. When the adapter is administered, it bridges the CAR-T cell to the cancer cell, forming an immunological synapse that triggers tumor lysis (Viaud et al., 2018, Oncotarget). This platform allows for the modulation of T-cell responses by adjusting the adapter dosage, potentially reducing the risk of severe cytokine release syndrome (Calibr-Skaggs, 2020). Additionally, it enables a single CAR-T cell product to be used against multiple different antigens by simply swapping the adapter molecule (NCT04450069).

Other names

Linker-Label-EpitopesCAR-T adapter epitopeSwitchable CAR-T neo-epitopePNE-tagged adapterBiotinylated adapter epitope

The CAR-T cell recognizes the synthetic PNE label on the adapter molecule. The adapter molecule simultaneously binds to a tumor-associated antigen (TAA) via its targeting domain (e.g., a Fab fragment). This dual binding creates an artificial immunological synapse, leading to T-cell activation, cytokine release, and directed lysis of the tumor cell.