OBJECTIVE: To develop a completely novel DNA peptide-combined vaccine and determine whether it can efficiently improve tumor-specific cytotoxic T lymphocyte (CTL) responses and inhibit tumor progression in experimental prostate cancer models.
METHODS: The DNA/peptide combined vaccine was prepared by the self-assembly of a cationic peptide ([K]18P9) containing 18 lysines and a CTL epitope peptide, prostate stem cell antigen (PSCA (14-22)) (HLA-A2 restricted) with a recombinant plasmid encoding human full-length PSCA gene (pcDNA3.1(+)-PSCA) through electrostatic interactions. The formation of a DNA/peptide complex was examined by DNA retardation assay, DNase I protection assay, and transmission electron microscopy. The efficacy of vaccination using this complex was demonstrated in terms of the PSCA-specific CTL activity and antitumor immunity to PSCA(+) tumors in a murine model.
RESULTS: This form of DNA/peptide complex could efficiently transfer the plasmid encoding full-length PSCA gene into mammalian cells and induced potent CTLs cytotoxicity against a human prostate carcinoma cell line established from the left supraclavicular lymph node metastasis from a 50-year-old man with prostate carcinoma in 1977. Expressing PSCA compared with pcDNA3.1(+)-PSCA, [K]18P9 peptide, or pcDNA3.1(+). Moreover, the vaccination of mice with this complex induced a potent antitumor immunity to prostate carcinomas in a xenograft tumor model in nude mice.
CONCLUSION: This study suggests that a specific antitumor immune response can be induced by this DNA/peptide combined vaccine, which represents a new strategy for use in the immunotherapy of prostate cancer.
Written by:
Zhang KQ, Yang F, Ye J, Jiang M, Liu Y, Jin FS, Wu YZ Are you the author?
Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
Reference: Urology. 2012 Jun;79(6):1410.e7-1410.e13
doi: 10.1016/j.urology.2012.02.011
PubMed Abstract
PMID: 22513035