Whitlow linker (218 linker) (218 linker)

The Whitlow linker, also known as the 218 linker, is a synthetic 18-amino acid peptide sequence (GSTSGSGKPGSGEGSTKG) specifically engineered to join the variable heavy (VH) and variable light (VL) domains of single-chain variable fragments (scFvs) (Whitlow et al., 1993). Unlike the common (Gly4Ser)3 linker, the Whitlow linker was designed to be more hydrophilic and resistant to proteolysis, thereby improving the solubility and reducing the aggregation of the scFv (Whitlow et al., 1993). In the field of adoptive immunotherapy, this linker is frequently incorporated into Chimeric Antigen Receptor (CAR) constructs to ensure the extracellular binding domain maintains high affinity for its target antigen (Goff et al., 2010). While the linker itself is not a therapeutic target, its structural properties are vital for the functional expression and stability of CAR-T cells on the cell surface. Research has indicated that the choice of linker can influence the immunogenicity of the CAR-T product, as the linker sequence may occasionally be recognized as a foreign epitope by the host immune system (Goff et al., 2010).

Other names

218 linkerWhitlow 218 linkerGSTSGSGKPGSGEGSTKG linkerWhitlow peptide

Acts as a flexible, hydrophilic bridge that facilitates the correct assembly and orientation of VH and VL domains in scFv-based receptors.