In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells

• Published in: Vaccine Vol. 35; no. 52; pp. 7240 - 7249
• Main Authors: Sales, Natiely S., Silva, Jamile R., Aps, Luana R.M.M., Silva, Mariângela O., Porchia, Bruna F.M.M., Ferreira, Luís Carlos S., Diniz, Mariana O.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 19.12.2017; Elsevier Limited
• Subjects: Antigen-presenting cells; Bioluminescence; CD8 antigen; Cell activation; Cervical cancer; Cytotoxic T cells; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA vaccine; DNA vaccines; Drug delivery systems; Effector cells; Electroporation; HPV-induced tumors; Human papillomavirus; Immune response; Immune response (cell-mediated); Immune system; Immunogenicity; Immunological memory; Immunomodulation; Immunotherapy; In vivo electroporation; Infiltration; Laboratory animals; Lymphocytes; Lymphocytes T; Melanoma; Memory cells; Metastases; Plasmids; Therapeutic vaccine; Tumor protection; Tumors; Vaccines; Viral infections; Viruses; HPV-induced tumors; DNA vaccine; Tumor protection; Therapeutic vaccine; Cytotoxic T cells; In vivo electroporation
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.11.011

In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8+ T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8+ T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines.