Fusion Protein Vaccines Targeting Two Tumor Antigens Generate Synergistic Anti-Tumor Effects
Journal
PLoS ONE
Date Issued
2013
Author(s)
Abstract
Introduction:Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein.Materials and Methods:In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed.Results:PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone.Conclusion:Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies. ? 2013 Cheng et al.
SDGs
Other Subjects
cancer vaccine; E6 tumor antigen; E7 tumor antigen; fusion protein vaccine; gamma interferon; peptide vaccine; tumor antigen; unclassified drug; animal cell; animal experiment; animal model; antibody response; antineoplastic activity; article; cancer immunization; cancer immunotherapy; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; drug potency; drug potentiation; drug research; drug targeting; enzyme linked immunosorbent assay; female; immunohistochemistry; in vitro study; in vivo study; mouse; nonhuman; protection; protein depletion; solid tumor; tumor immunity; tumor volume; Wart virus; Animals; Antibodies, Viral; Antigens, Neoplasm; Antigens, Viral; Cancer Vaccines; Cytokines; Female; Human papillomavirus 16; Humans; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Papillomavirus Infections; Papillomavirus Vaccines; Recombinant Fusion Proteins; Repressor Proteins; Tumor Burden; Uterine Cervical Neoplasms; Vaccination
Type
journal article