Immunotherapy for Cervical Cancer---Translational Research

The human papillomaviruses (HPV) are small DNA tumor viruses that infect epithelial cells and induce proliferative lesions. Substantial epidemiologic data along with in vitro and in vivo studies have led to the implication of particular HPVs with the development of epithelial malignancies. More than 90% of cervical cancer specimens contain HPV genomes, particularly type 16 and 18, and the viral transforming proteins, E6 and E7, are consistently expressed in cervical cancer cell lines and HPV-associated neoplasms. Thus, E6 and E7 represent true tumor-specific antigens and allow for the development of immunotherapeutic strategies to combat HPV-associated cancers. The long-term objective of this proposal is to build an immunotherapy program against cervical cancer and to translate novel therapeutic immunotherapeutic approaches from the laboratory to the clinics. In the current proposal, we will focus our basic discovery—codon optimized GM-CSF gene enhance the immune responses and prolongs life span of treated animal—into translational research. We will apply micro PET and micro SPECT in vivo imaging modality to evaluate the immune responses and tumor regression in small animal model with reporter gene of NFAT-TKGFP(nuclear factor of activated T- lymphocytes thymidine kinase-green fluorescence protein). To achieve this goal: Three SPECIFIC AIMS are proposed: Specific Aim 1: Determination of Anti-tumor activity of novel codon optimized GM-CSF augmented tumor cell vaccines via non-invasive imaging system in tumor-bearing animal models. Specific Aim 2: In vitro generation of HPV-specific cytotoxic T lymphocytes by novel codon optimized GM-CSF augmented tumor cell vaccines for immunotherapy. Specific Aim 3: Development of a combination therapy with immunotherapy and chemotherapy. Success of this proposal will help develop effective therapeutic approach to treat cervical cancer.

Project ID:PC9808-0575
External Project ID:NSC98-2314-B182-049