Abstracts

Treatment with adjuvant-free fusion protein comprised of M. bovis BCG Hsp65 and HPV16 E7 induces cell-mediated anti-tumor immunity.

Chu N.R., Wu B., Bantroch S., Sweet H., Boux L., Siegel M., Mizzen, L.

Stressgen Biotechnologies Corporation, Victoria, BC, Canada

Abstract presented at AAAAI 56th Annual Meeting - San Diego, CA March 3-8, 2000 as printed in J Allergy Clin Immunol 105 (1 part 2): S115

Infection of the anogenital mucosa with one of a subset of "high-risk" human papillomaviruses (HPV) has been clearly established as being necessary for the induction of cervical and anal intraepithelial neoplasia and cancer. Of the approximately 100 types of HPV, the presence of HPV16 has been identified as being associated with all of the aforementioned conditions.
Viral infection of epithelial cells leads to sustained expression of the early gene products E6 and E7, which in turn promote cellular transformation via p53 and Rb interactions, respectively. Because it is continuously expressed in transformed cells and is immunogenic, E7 is an ideal candidate tumor antigen for immunotherapy. We have shown previously that the administration of a recombinant fusion protein comprised of M. bovis BCG Hsp65 covalently linked to HPV16 E7 (HspE7) is capable of providing prophylaxis and therapeutic treatment in the murine TC-1 cervical carcinoma model (Chu et. al., submitted for publication).

Based on these findings, we have initiated clinical trials involving the use of HspE7 for the treatment of cervical intraepithelial neoplasia. In the present study we compare antibody and cytokine induction to the E7 antigen following immunization with E7 alone or HspE7. In addition, to identify which lymphocyte subset (i.e. CD4 or CD8) is responsive to HspE7, we have used CD8 and MHC class II "knockout" mice in the TC-1 model. The results are consistent with the ability of HspE7 to induce cell-mediated immunity leading to the rejection of tumor. These findings are in agreement with other data describing the use of Hsp fusion proteins for the induction CTL responses and support our efforts to use HspE7 in the clinic for the treatment of cervical and anal intraepithelial neoplasia.

We thank Dr. T.C. Wu (Johns Hopkins University, Baltimore, MD) for providing the TC-1 cell line.