IL-6-encoding tumor antigen generates potent cancer immunotherapy through antigen processing and anti-apoptotic pathways.
A naked DNA vaccine delivered by gene gun into antigen-presenting cells (APCs) has emerged as an attractive strategy for antigen-specific cancer immunotherapy. However, APCs have a limited lifespan, hindering their long-term ability to prime antigen-specific T cells. Furthermore, the potency of DNA vaccines is limited by their inability to process and present antigens. Interleukin-6 (IL-6) could play a role in immunity and cell apoptosis. We explored how the DNA vaccine encodes IL-6 to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7. Mice vaccinated with IL-6/E7 DNA exhibited dramatic increases in E7-specific T-cell immunities, anti-E7 antibody responses, and impressive anti-tumor effects against E7-expressing tumors. The in vitro results revealed that IL-6 enhances DNA vaccine potency through the major histocompatibility complex class I pathway via direct and cross-priming effects. In addition, the delivery of IL-6/E7 DNA prolonged the survival of transduced dendritic cells (DCs) in vivo. Our results indicated that the IL-6/E7 DNA vaccine combined the mechanisms of enhancing antigen processing and presentation with prolonging the survival of DCs. Using IL-6 represents an innovative approach to enhancing DNA vaccine potency and holds promise for cancer prevention and immunotherapy.
Hsieh
Chang-Yao
CY
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Chi-An
CA
Huang
Chia-Yen
CY
Chang
Ming-Cheng
MC
Lee
Chien-Nan
CN
Su
Yi-Ning
YN
Cheng
Wen-Fang
WF
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D000951:Antigens, Neoplasm; D017931:DNA Primers; D015850:Interleukin-6; D019444:Vaccines, DNA