Immunotherapy involving the E7 oncoprotein and glycoprotein D (gD) of herpes virus in vaccine formulations designed to control papillomavirus-associated tumors

Abstract

Cervical cancer is considered a major public health problem and a major cause of tumor-related deaths in women. Virtually all cases of cervical cancer, as well as an increasing proportion of tumors in the anal and head / neck areas, are associated with infection by human papillomavirus (HPV), of which the genotypes HPV-16 and 18 are the most commonly related to these tumors. In this project we will explore a therapeutic vaccine strategy against these tumors using a recombinant form of HPV-16 E7 oncoprotein fused to the glycoprotein D (gD) of HSV-1, a protein with properties of endogenous adjuvants, particularly for CD8 + T lymphocytes. The recombinant protein will be produced in Escherichia coli and insect cells infected with baculovirus for further purification. The recombinant protein will be tested as subunit vaccines for parenteral administration in combination with different adjuvants and immunomodulatory agents. The therapeutic properties of the vaccine formulations will be evaluated in mice challenged with TC-1 cells which express the E6 and E7 oncoproteins of HPV-16. The E7-specific immune responses mediated primarily by CD8 + T lymphocytes will also be measured. The results obtained during the execution of this project should contribute to the development of a novel vaccine strategy for the control of tumors induced by HPV-16. (AU)