Abstract A62: In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors

Cervical cancer associated with persistent papilloma virus infections (HPV) is a public health problem and represents the third most frequent type of cancer in women. Our group developed a DNA vaccine against HPV-induced tumors based on the expression of the HPV-16 E7 oncoprotein genetically fused to the HSV-1 glycoprotein D (gD) (pgDE7h). This vaccine is capable of promoting antitumoral effects against tumor cells expressing HPV-16 E6 and E7 proteins (TC-1 cells) and induces specific cellular immune responses. In view of the low success rate of DNA vaccines in clinical trials, in vivo electroporation (EP) is a promising strategy for plasmid delivery, leading to increased cellular transfection and enhanced immune responses. In this study, C57BL/6 mice were inoculated with TC-1 cells subcutaneously and immunized 3 days later with pgDE7h intramuscularly, associated or not with EP. Immune responses were analyzed 14 days after vaccination and tumor growth was monitored for 60 days. Similar antitumor effects were obtained with 10-fold less DNA associated with EP when compared to the group that was inoculated only with DNA, reaching around 20% of tumor-free mice. Dose-response curves indicated that maximum protective immunity was achieved with 50 ug of vaccine inoculated with EP, promoting 100% of antitumor protection. This group also had enhanced frequencies of cytotoxic lymphocytes expressing the degranulation marker CD107a and high in vivo cytotoxic activities. Besides that, a delayed vaccination performed 10 days after the TC-1 injection led to 70% of tumor-free mice until the end of the observed period. Collectively, these data confirmed that EP can be used as an efficient method of DNA vaccine delivery and should be further studied to improve the chances of cancer vaccine success in clinical trials. Citation Format: Natiely Silva Sales, Mariana de Oliveira Diniz, Jamile Ramos Silva, Mariângela de Oliveira Silva, Bruna F. M. M. Porchia, Luana R. M. M. Aps, Luis Carlos Souza Ferreira. In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors [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; Sao Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A62.