Epitopes described in "HPV16E7 tumor antigen modified by KDEL sequence induce specific cytotoxic T lymphocytes-dependent antitumor immunity."

Article Authors:Rui Yin; Wenjie Zheng; Fei Hao; Xi-Chuan Yang; Bai-Yu Zhong; Qin-Jie Li
Article Title:HPV16E7 tumor antigen modified by KDEL sequence induce specific cytotoxic T lymphocytes-dependent antitumor immunity.
Reference Detail
Reference ID:1017715
Abstract:BACKGROUND: Infection by high-risk HPV (human papillomavirus) is the primary cause of cervical cancer. Dendritic cell-based (DC-based) therapeutic vaccine represents a promising approach to the prevention and treatment of many cancers, including HPV-related cancers, but current strategies have met with only limited success in preclinical and clinical research. It is necessary to find a properly and effective antigen presenting system of DC-based vaccine. OBJECTIVE: To design a new HPV16 therapeutic vaccine using an endoplasmic reticulum (ER) retrieval signal and study its ability to induce the specific CTL activity in vitro and in vivo. METHODS: E7(p)-KDEL and its control peptide were synthesized on solid phase. A series of methods were used, including standard (51)Cr-labeled release assay, enzyme-linked immunospot (ELISPOT) assay and ELISA, to detect the CTL activity induced by different peptides. Prophylactic models and therapeutic models were examined to detect the in vivo effectiveness of E7(p)-KDEL-loaded DCs. RESULTS: The specific CTL activity induced by E7(p)-KDEL-loaded DCs was much stronger than that induced by the other peptide-loaded DCs. Comparing with the control peptides, after incubation with the spleen cells of mice, the E7(p)-KDEL-loaded DCs could induce higher concentration of secreted IFN-gamma and had higher ELISPOT numbers. In animal models, E7(p)-KDEL-loaded DCs vaccines effectively protected mice against fatal TC-1 tumor challenge and cured tumor-bearing mice. CONCLUSIONS: The ER retrieval signal-mediated antigen delivery system may have important clinical application for cancer therapy, even virus infectious disease and autoimmune disease.
Affiliations:Department of Dermatology, Southwest Hospital, Third Military Medical University, District Shapinba, Chongqing 400038, China. swyinrui@163.com
Reference Type:Literature
PubMed ID:19500947
Journal:J Dermatol Sci
Journal Volume:55
Article Pages:116-22
Journal ISSN:0923-1811
Article Chemical List:Cancer Vaccines;HLA-A2 Antigen;Oligopeptides;Oncogene Proteins, Viral;Papillomavirus E7 Proteins;Papillomavirus Vaccines;Protein Sorting Signals;oncogene protein E7, Human papillomavirus type 16;lysyl-aspartyl-glutamyl-leucine;Interferon-gamma
Article MeSH List:Animals; Cancer Vaccines(immunology); Cell Line, Transformed; Dendritic Cells(immunology; transplantation); Drug Design; Female; HLA-A2 Antigen(immunology); Immunity, Cellular; Immunotherapy, Adoptive; Interferon-gamma(metabolism); Lymphocytes, Tumor-Infiltrating(immunology); Mice; Mice, Inbred C57BL; Neoplasms, Experimental(immunology; prevention & control; therapy; virology); Oligopeptides(immunology); Oncogene Proteins, Viral(immunology); Papillomavirus E7 Proteins; Papillomavirus Vaccines(immunology); Protein Sorting Signals; T-Lymphocytes, Cytotoxic(immunology); Th1 Cells(immunology); Time Factors
Curation Last Updated:2015-07-30 20:34:26