Cervical cancer is one of the most common cancers in women world-wide. Most, if not all, contain human papillomavirus (HPV) DNA and the HPV types present are a subgroup of HPV types associated with benign or premalignant genital lesions. The cancers evolve from premalignant lesions of the cancer associated subgroup. In cancer, as well as in cancer derived cell lines, viral DNA continues to be transcribed which encodes the two early proteins, E6 and E7. The cottontail rabbit papillomavirus (CRPV) and the neoplasias induced by it provide an animal model to study the interactions between host, virus and the evolving neoplasias. CRPV induces benign tumors (papillomas) in the keratinizing epithelium of domestic and cottontail rabbits (the natural host). Papillomas may regress spontaneously or persist and progress to invasive and metastasizing cancers at a high frequency, particularly, in domestic rabbits. As in the human cancers, mRNA for the E6 and E7 proteins are the most abundant in rabbit cancers. Our long-term goal is to elucidate in a broad sense various host interaction in the rabbit system.
The specific aims are: 1. Characterization of the immune status a. During papilloma development. b. During spontaneous regression. c. During development of cancers. By; i) The analysis of serum for antibodies to nonstructural viral proteins. ii) Checking for CRPV specific cytotoxic T cell lymphocytes (CTL) and mapping viral epitopes recognized by these cells. iii) Determination of the lymphoproliferative (T cell) response to viral peptides or proteins, to extracts from virus or carcinogen (DMBA) induced papillomas or to cells expressing viral proteins. iv) Measuring delayed type hypersensitivity. 2. Characterization of papilloma and carcinoma cells with respect to the expression of viral and auxiliary proteins (MHC and ICAM) required for immune recognition. 3. Modification of the immune response a. Before challenge with virus or viral DNA b. During papilloma development. c. After progression to carcinomas. By; i) Immunization with recombinant vaccinia virus expressing nonstructural or structural CRPV proteins. ii) Immunization with vaccines prepared from virus or DMBA induced tumors. iii) Administration of cytokines.
