New therapeutic frontiers against tumors caused by human papilloma virus (HPV): experimental evaluation of the chemotherapy in association to vaccine strategies

Abstract

Human papilloma virus (HPV) is responsible for 99,7% of cervical cancer cases and approximately 5% of all cancers worldwide, and HPV-16 is the main etiological agent of this disease. The development of therapies to control HPV-induced tumors searches the establishment of a new treatment based on immunotherapy that is advantageous compared with traditional invasive and aggressive procedures. In the field of immunotherapy, DNA vaccines represent a simple and promising strategy against HPV-associated tumors based on generating immune response against proteins known to be essential for malignant cell transformation. To potentiate this effect, the present project proposes the investigation of cisplatin association, the main chemotherapeutic drug currently used against cervical cancer to the vaccine plasmid pgDE7h that encodes E7 protein of HPV-16 fused to gD protein of Herpes Simplex Virus (HSV-1). The project also proposes the use of the formulation encapsulated in vesicles, of lipid or peptide nature, with goal of increasing the therapeutic efficacy of the vaccine and reduce the deleterious effects of the chemotherapy. The experiments will be based on the implantation of tumoral cell line (TC-1) in C57BL/6 mice and the therapeutic efficacy will be evaluated through monitoring of tumor regression and the cellular response induced by the combined therapy, including T lymphocytes CD4 + and specific CD8 + and production of important cytokines for the proliferative and cytotoxic activities, such as IL-2 and IFN-g. (AU)