Whitlow linker epitope (Whitlow linker)

The Whitlow linker epitope, also known as the 218 linker, is a synthetic 18-amino acid peptide sequence (GSTSGSGKPGSGEGSTKG) designed to connect the variable heavy (VH) and variable light (VL) chains of a single-chain variable fragment (scFv) with high proteolytic stability and low tendency for aggregation (Whitlow et al., 1993, Protein Engineering). In Chimeric Antigen Receptor (CAR) T-cell therapy, this linker is a common component of the extracellular antigen-binding domain, particularly in constructs targeting CD19. Because the sequence is distinct from native human proteins, it functions as a unique tag that can be targeted by specialized monoclonal antibodies for monitoring CAR-T cell expansion and persistence in clinical settings (Miltenyi Biotec, 2024). Beyond diagnostics, the Whitlow linker is investigated as a target for therapeutic off-switches, where anti-linker antibodies could be administered to deplete CAR-T cells in patients experiencing severe toxicities such as cytokine release syndrome (Zheng et al., 2012, Journal of Translational Medicine). However, the non-native nature of the Whitlow linker can also provoke an immune response, such as anti-drug antibodies, which may lead to the rejection of the CAR-T cells and limit their long-term efficacy (Maus et al., 2014, Blood).

Other names

218 linkerWhitlow 218 linkerGSTSGSGKPGSGEGSTKG peptidescFv 218 linker

Provides a specific binding site for monoclonal antibodies to enable the detection, enrichment, or antibody-mediated depletion of CAR-T cells.