Abstracts

Cancer Immunotherapy using adjuvant-free, fusion protein encoding M. bovis BCG hsp65 and HPV16 E7

Abstract presented at International Conference on Dynamics and Regulation of the Stress Response  -  Kyoto, Japan  March 9-12, 1998

Chu NR, Wu HB, Bantroch S, Wu TC, Boux L, Siegel M, Mizzen LA

More than ninety percent of cervical cancer specimens contain human papillomavirus (HPV) genomes, particularly type 16, and the viral transforming proteins, E6 and E7, are consistently expressed in cervical cancer cell lines and in HPV-associated cancers.  Using E7 as the tumor-specific antigen, we are designing vaccines and immunotherapeutic strategies for HPV-related cervical cancers.  As a model, the TC-1 tumor cell line (cotransformed by c-Ha-ras and HPV16 E6/E7), is being used to study the in vivo efficacy of a novel immunogen, Hsp65E7, on TC-1 tumor rejection. Hsp65E7 is a recombinant fusion protein consisting of M. bovis BCG hsp65 and HPV16 E7.  Immunization of mice with Hsp65E7 in saline elicited both a lymph node proliferative response to E7 which was inhibitable by anti-MHC class II antibody and CTL which lyzed TC-1 cells.  Antibodies specific for E7 were also generated.  Prophylactic immunization with Hsp65E7 in saline provided protection to C57BL/6 mice injected with subcutaneous tumor challenge.  Therapeutic Hsp65E7 immunization of mice carrying tumor resulted in complete tumor regression.  Furthermore, the immune response arising from therapeutic immunization protected the animals from a subsequent challenge with TC-1.  Lastly, in a direct comparison with HPV16 E7 recombinant protein, Hsp65E7 immunization was superior in its ability to regress the tumor.  Taken together, the findings suggest that administration of adjuvant-free, Hsp65E7 fusion protein induces cellular anti-tumor immunity which results in the regression of established tumor.