title: DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice.
abstract: The ideal immunological target for cancer vaccine development would meet the criteria of tumor specificity, immunogenicity and vital dependency of the tumor on the functional activities of the antigenic target so as to avoid antigenic loss by mutation. Given that at face value the brother of regulator of imprinted sites (BORIS) transcription factor meets these criteria, we have developed a mutant variant of this molecule (mBORIS) that lacks tumorigenic ability, while retaining immunogenic epitopes that elicits responses against histologically irrelevant tumor cells. Here we compared vaccine strategies employing as an immunogen either mBORIS recombinant protein formulated in a strong Th1-type adjuvant, QuilA or DNA encoding this immunogen along with plasmids expressing interleukin (IL)12/IL18 molecular adjuvants. In both groups of vaccinated mice induction of tumor-specific immunity (antibody response, T-cell proliferation, cytokine production, T-cell cytotoxicity) as well as ability to inhibit growth of the aggressive breast cancer cell line and to prolong survival of vaccinated animals have been tested. We determined that DNA, but not recombinant protein vaccine, induced potent Th1-like T-cell recall responses that significantly inhibited tumor growth and prolongs the survival of vaccinated mice. These studies demonstrate that DNA immunization is superior to recombinant protein strategy and provide a clear guidance for clinical development of a cancer vaccine targeting what appears to be a universal tumor antigen.
authors.affiliation: Department of Molecular Immunology, The Institute for Molecular Medicine, Huntington Beach, CA 92647-3652, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mkrtichyan
authors.forename: A
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: D
authors.initials: D
authors.lastname: Loukinov
authors.forename: H
authors.initials: H
authors.lastname: Davtyan
authors.forename: T E
authors.initials: TE
authors.lastname: Ichim
authors.forename: D H
authors.initials: DH
authors.lastname: Cribbs
authors.forename: V V
authors.initials: VV
authors.lastname: Lobanenkov
authors.forename: M G
authors.initials: MG
authors.lastname: Agadjanyan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D062605:Quillaja Saponins; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; D020382:Interleukin-18; D062605:Quillaja Saponins; D011994:Recombinant Proteins; D012503:Saponins; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; C046386:Quil A; D007371:Interferon-gamma