Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccineactivity
Xy. Wang et al., Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccineactivity, J IMMUNOL, 166(1), 2001, pp. 490-497
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.