Abstracts

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

Abstract presented at Experimental Biology 98  -  San Francisco, CA  April 18-22, 1998 as printed in FASEB J  1998  12(5 part 2): A909

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

Human papillomavirus (HPV) 16 infection has been identified as the causative agent of cervical dysplasia and cervical cancer. A hallmark of persistent infection is the continuous expression of HPV16 E6 (E6) and HPV16 E7 (E7) in the epithelial cells of the cervix.  These oncoproteins contribute to the transformation process.  Because of their continued presence and their integral role in perpetuating malignancy, E6 and E7 are ideal candidates as tumor antigens for immunotherapy.  Using the TC-1 tumor cell line, (co-transformed by c-Ha-ras and HPV16 E6/E7), as a model for cervical cancer, we have studied 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 and CTL activity against TC-1.  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.  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.