Targeting antigens to dendritic cells as an immunotherapeutic strategy to control HPV-induced tumors

Abstract

Cervical cancer is considered a major public health problem and is one of the leading causes of cancer death in women. Virtually, all cases of cervical cancer, as well as growing evidences of anal tumors and head and neck cancer, are associated with human papillomavirus (HPV) infections, mainly by the HPV-16, the genotype most commonly related to tumors. The viral proteins E6 and E7 are responsible for cellular malignization and are present in all transformed cells and, therefore, represent ideal targets for the development of antigen-specific therapeutic approaches. In this project, we will explore an immunotherapeutic strategy against these tumors using the HPV-16 E7 oncoprotein fused to the anti-DEC205 antibody. The antibodies will be produced from the culture supernatants of transfected HEK293T eukaryotic cells. The anti-DEC205 hybrid antibodies will be tested by parenteral or mucosal administration combined with the adjuvant Poly I: C. The therapeutic properties of the formulation will be evaluated in mice transplanted with TC-1 cells that express the HPV-16 E6 and E7 oncoproteins, following subcutaneous cell injection or mucosal tumor cell graft. The induction of E7-specific immune responses mediated primarily by T CD8+ lymphocytes will be evaluated. The results obtained during this project will contribute to the development of a novel immunotherapeutic strategy to control tumors associated with HPV-16. (AU)