Heat shock protein 70-derived TKD peptide (TKD peptide)

The Hsp70-derived TKD peptide is a 14-amino acid sequence (TKDNNLLGRFELSG) corresponding to the C-terminal domain of the 70 kDa heat shock protein (Hsp70), specifically the HSPA1A isoform. While Hsp70 is primarily an intracellular chaperone, it is frequently overexpressed and localized to the plasma membrane of various malignant tumor cells, where it serves as a tumor-specific marker. The TKD peptide acts as an immunostimulatory ligand that specifically activates Natural Killer (NK) cells by binding to the CD94 receptor. This activation enhances the NK cells' ability to recognize and kill membrane-Hsp70-positive tumor cells through the release of perforin and granzyme B. In clinical settings, the peptide is often used ex vivo to prime patient-derived NK cells or administered in combination with cytokines like IL-2 to treat advanced solid tumors, including lung and colorectal cancers. Its high specificity for tumor-associated Hsp70 makes it a promising tool for targeted immunotherapy with minimal impact on healthy tissues.

Other names

TKDNNLLGRFELSGHsp70 C-terminal peptideHsp70-derived 14-mer peptideTKD

The TKD peptide mimics the C-terminal domain of membrane-bound Hsp70 (mHsp70) and binds to the C-type lectin receptor CD94 on Natural Killer (NK) cells. This interaction, typically in the presence of low-dose IL-2, triggers the activation, proliferation, and increased cytolytic activity of NK cells against mHsp70-positive tumor cells. It also enhances the migratory capacity of NK cells toward tumor sites by upregulating chemokine receptors.