Development of novel immuno-gene therapy for gastrointestinal cancer using antigen presenting function of heat shock protein

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The anti-tumor effect of heat-shock proteins (hsp) derived from CMS7-ME tumor was investigated. CMS7-ME, cell line was established by a HER2/neu transduction into the CMS7 derived from BALB/c mice fibrosarcoma. Three kinds of hsps, gp-96, hsp-70, hsp-90 were extracted from CMS7-ME and subcutaneously inoculated into the other mice. CMS7-ME tumor was implanted into these hsp-immunized mice. In gp96 or hsp-70 treated group, growth inhibitory effect implanted of CMS7-ME was observed. There is no anti-tumor effect in hsp-90 treated group.In the model of CT-26, N-nitroso-N-methylurethane induced BALB/c colonic tumor, an anti-tumor effect of CT-26 derived hsps was investigated, gp-96 derived from CT-26 showed growth inhibitory effect to CT-26 tumor. There is no growth inhibitory effect of CT-26 derived hsp-70 or hsp-90 treated groups. The complex of gp96 extracted from normal liver and CT-26 specific peptide, AH-1 showed anti-tumor effect in this model. However an induction of AH-1 specific cytotoxic T cells was not detected in this experiment.Anti-tumor effect of dendritic cells (DC) pulsed with gp96 derived from CT-26 was compared with that of DC pulsed with AH-1. DC pulsed with gp96 derived from CT-26 showed more significant growth inhibitory effect to CT-26 tumor in comparison with AH-1 pulsed DC.These results suggest that the role of tumor derived hsp in the antigen presenting process.Further investigation would be required to confirm the mechanisms of these effects as a pre-clinical investigation.