Co-expression of IL-10 receptor as a strategy to enhance the effects of a DNA vaccine focused on the control of tumors induced by HPV-16

Abstract

The Laboratory for Vaccine Development (LDV) of USP created a therapeutic vaccine strategy for cervical cancer that employs a vector encoding the E7 protein of HPV-16 fused to glycoprotein D (gD) of herpes simplex virus type 1 (HSV -1). The pgDE7h DNA vaccine showed preventive and therapeutic properties in mice when they are challenged with TC-1 cells which express E6 and E7 oncoproteins of HPV-16. The goal of this project is evaluate the effects of administration of a plasmid encoding the soluble receptor of IL-10 (pIL10R) in improve of DNA vaccine pgDE7h in the control of tumors induced by HPV-16. This proposal seeks to reduce the immunosuppression mediated by IL-10 in tumor immune evasion. To do so will be testing different vaccine regimens. Initially, we will evaluate the therapeutic potential of tumor regression in the combined vaccine varying the time interval between the animal challenge with TC-1 cells and the administration of the vaccine. Afterwards, the dose of the vaccine will be gradually reduced in the pursuit of its minimum amount capable of inducing therapeutic protection. The response of E7-specific T lymphocytes triggered by the vaccine will be determined by different experimental approaches. Furthermore, the effect of the vaccine will be assessed by the expansion of immunosuppressive cells as regulatory T cells and myeloid suppressor cells as well as the cytokine profile. Subsequent, the role of IL-10 in mice deficient for the gene will be found after the administration of the vaccine pdDE7h. The results obtained during the execution of this project will contribute to the development of a novel vaccine strategy that can act both in inducing an anti-tumor response as the control of immunosuppression. (AU)