Methods of Purification of Heat Shock Protein-Peptide Complexes for Use as Vaccines Against Cancers

Immunization of mice, with preparations of heat shock proteins (HSPs) isolated from tumors or virus-infected cells, has been shown to elicit specific protective immunity against the tumor or the virus-infected cells used as the source of the HSP. This phenomenon has been shown to be general, in that specific immunogenicity of tumor-derived HSP preparations has been demonstrated in the cases of hepatoma (1 ), fibrosarcoma (2 -8 ), lung carcinoma (9 ), prostate cancer (10 ), spindle cell carcinoma (9 ), colon carcinoma (9 ), and melanoma (9 ), in mice and rats of different haplotypes. These tumors include chemically induced (1 -8 ), UV-induced (11 ) and spontaneous tumors (9 ), and efficacy has been demonstrated in prophylactic (1 -8 ,10 ,11 ) as well as in therapeutic models (9 ). In the case of viral models, HSP preparations from cognate cells have been shown to elicit a virus-specific cellular immune response against influenza virus (12 ), SV40 (13 ), vesicular stomatitis virus (14 ) and lymphocytic choriomeningitis virus (15 ). HSP preparations from cells transfected with model antigens (Ags) such as ovalbumin and β-galactosidase have been shown to elicit Ag-specific cytotoxic T-lymphocytes (CTL)s against ovalbumin (16 ) or β-galactosidase, respectively (17 ) The immunogenicity of HSP-peptide complexes has obvious applications in vaccination against cancers and infectious diseases (18 ). With respect to cancers, HSP-peptide complexes isolated from a patient’s cancer can serve as customized, patient-specific therapeutic vaccines (19 ).