Abstract A65: In vivo neutralization of IL-10 enhances the antitumor effects of a therapeutic vaccine against HPV-associated tumor

Abstract

Abstract Although experimental therapeutic vaccines against HPV-induced tumors are capable of activating systemic E6 and E7-specific CD8+ T cells and inducing high levels of antitumor protection in murine model, they do not always correlate with clinical efficacy once these vaccines are tested in clinical settings. This observed discrepancy can be attributed to an immunosuppressive microenvironment elicited by the tumor that limits the efficacy of immunotherapeutic approaches. Solid evidence shows that IL-10 cytokine secretion is a relevant mediator of tumor immune evasion mechanisms, which inhibits the function of CD8+ T cells. Our group has sought alternatives to potentiate the effect of a DNA-based therapeutic vaccine (pgDE7h), which encodes the HPV-16 E7 protein fused to the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD), previously developed in our laboratory. The present study aimed to investigate the potential role of immunossupression restriction using a plasmid encoding the soluble IL-10 receptor (pIL10R) to enhance the pgDE7h vaccine potency in the control of tumors expressing HPV-16 E6 and E7 proteins in a murine model (TC-1 cells). Our results showed a tumor growth delay after combining the vaccine with pIL-10R. Additionally, the use of in vivo electroporation as the plasmids delivery method conferred a therapeutic protection of 90% and 60% when the animals were immunized 5 or 14 days after challenge, respectively. The combination of the plasmids was also capable of increasing substantially the numbers of activated E7-specific CD8+ T lymphocytes both systemically and at the tumor site. Altogether, the results obtained are promising for the development of new strategies to increase the antitumor therapeutic effects of the pgDE7h vaccine and may contribute to its use under clinical conditions. Note: This abstract was not presented at the conference. Citation Format: Jamile Ramos da Silva, Natiely Silva Sales, Mariangela de Oliveira Silva, Luana M. M. Aps, Luis Carlos de Souza Ferreira, Mariana de Oliveira Diniz. In vivo neutralization of IL-10 enhances the antitumor effects of a therapeutic vaccine against HPV-associated tumor [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A65.