Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model

Tumor-derived purified heat shock protein (HSP), gp96, has tumor protective effect in a number of experimental cancers that include fibrosarcoma, hepa toma, and spindle cell carcinoma. The rationale for using gp96 as a vaccina ting agent stems from the discovery that HSPs, including gp96, chaperone an tigenic peptides for eventual recognition and elicitation of an immune resp onse. The immune response generated by the HSP-peptide complex is specific to the tumor from which they are derived The long-term objective nf our stu dies is to develop a vaccine for primary and metastatic prostate cancer usi ng tumor-derived HSPs. In the present study, we report our results on the t umor protective effect of irradiated Dunning G cells, or purified preparati ons of g96-peptide complexes as a tumor vaccine. Tumor incidence, latency, and tumor growth were the end points of measurement. Tumor bearing Copenhag en rats, made free of disease by surgical resection of the tumors resisted a fresh challenge of live Dunning G tumor cells. Vaccination with irradiate d whale cells failed to elicit any resistance to tumor growth. Vaccination with Dunning G derived purified gp96-peptide complexes delayed both inciden ce and growth of Dunning G induced tumors. Inhibition of tumor growth was o bserved when gp96 was administered after tumor induction. Our data suggests that tumor derived gp96-peptide complexes can be used as an effective prop hylactic and therapeutic agent even in poorly immunogenic cancer such as pr ostate cancer. Further investigations will determine specificity of action and define the immunological determinants and experimental conditions for i ts optimal activity.