Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccineactivity

Several studies have confirmed that certain stress proteins can function as potent vaccines against a specific cancer when purified from the same tumo r. Recent studies of two long-recognized but unstudied stress proteins, hea t shock protein (hsp) 110 and glucose-regulated protein (grp) 170, have sho wn them to be efficient peptide chain-binding proteins. The present investi gation examines the vaccine potential of hsp110 and grp170, First, it is sh own that prior vaccination with hsp110 or grp170 purified from methylcholan threne-induced fibrosarcoma caused complete regression of the tumor. In a s econd tumor model, hsp110 or grp170 purified from Colon 26 tumors led to a significant growth inhibition of this tumor. In addition, hsp110 or grp170 immunization significantly extended the life span of Colon 26 tumor-bearing mice when applied after tumor transplantation. A tumor-specific cytotoxic T lymphocyte response developed in the mice immunized with tumor-derived hs p110 or grp170, Furthermore, treatments of the mice with bone marrow-derive d dendritic cells pulsed with these two proteins from tumor also elicited a strong antitumor response. Last, we showed that mild, fever-like hyperther mic conditions enhance the vaccine efficiency of hsp110 as well as heat sho ck cognate 70, but not grp170. These studies indicate that hsp110 and grp17 0 can be used in hsp-based cancer immunotherapy, that Ag-presenting dendrit ic cells can be used to mediate this therapeutic approach, and that fever-l evel hyperthermia can significantly enhance the vaccine efficiency of hsps.