The human papillomavirus (HPV) is etiologically related to most cases of cervical cancer. The E6 and E7 genes of HPV is etiologically related to most cases of cervical cancer. The E6 and E7 genes of HPV attractive tumor-associated antigens for immunotherapy and several trials of therapeutic vaccines for cervical cancer are underway. The results to date have been only marginally successful since most patients apparently default to a T-helper type 2(Th2) response rather than a potentially more efficacious T-helper type (Th1) response. The eukaryotic initiation factor of Leishmania braziliensis (LeIF) is a potent and specific Th1 stimulator. It hypothesized that a vaccine containing the HPV proteins E 6 and/or E7 and utilizing the adjuvant LeIF will elicit a Th1 response to HPV associated tumors. To test this hypothesis, the following experiments will be performed: 1. The ability of LeIF to overcome the inherent Th2 preference of BALB/c mice will be determined. In addition, a comparison of LeIF with other adjuvant formulations will be performed. 2. The ability of HPV vaccinated BALB/c mice to reject autologous tumor cells tranfected with genes encoding HPV antigents will be determined. The effects of viral amino acid sequence variation in the E6 and E7 proteins will be assessed. 3. The ability of HPV vaccine-stimulated human peripheral blood mononuclear cells (PBMC's) to lyse autologous tumor in SCID mice will be determined. The significance of the specific aims lies in their potential to lead to phase I trial of a therapeutic vaccine for cervical cancer. This system has implications not only for cervical cancer but it may also lead to immunotherapeutic method to treat other immuunogenic cancers.
