Heat shock 70 kDa protein 1A (membrane-bound) (mHsp70)

Heat shock 70 kDa protein 1A (Hsp70) is a molecular chaperone that is typically localized within the cytosol and nucleus of healthy cells, where it assists in protein folding and protects against cellular stress. However, in a wide variety of malignant tumors, Hsp70 is specifically translocated to the plasma membrane, presenting an extracellular motif that is absent in normal tissues. This membrane-bound form (mHsp70) serves as a highly specific tumor antigen and a marker of aggressive disease, contributing to lysosomal stability and resistance to apoptosis. In the context of oncology, mHsp70 is a therapeutic target for monoclonal antibodies like cmHsp70.1 and for the activation of Natural Killer (NK) cells using Hsp70-derived peptides such as TKD. Because mHsp70 is found on approximately 50-70% of various cancer types—including lung, colon, and breast carcinomas—but not on normal cells, it provides a unique window for targeted immunotherapy and diagnostic imaging. Drugs targeting mHsp70 aim to exploit its role as a recognition site to trigger immune-mediated destruction of tumor cells while sparing healthy tissue.

Other names

HSPA1AHsp70-1Hsp72Membrane-associated Hsp70Heat shock 70 kDa protein 1

Targeting membrane-bound Hsp70 typically involves antibody-dependent cellular cytotoxicity (ADCC), activation of Natural Killer (NK) cells via the TKD peptide, or utilizing the protein as a docking site for the targeted delivery of radionuclides or toxins. Additionally, mHsp70 can be targeted to induce granzyme B-mediated apoptosis in tumor cells.