title: Enhancement of survivin-specific anti-tumor immunity by adenovirus prime protein-boost immunity strategy with DDA/MPL adjuvant in a murine melanoma model.
abstract: As an ideal tumor antigen, survivin has been widely used for tumor immunotherapy. Nevertheless, no effective protein vaccine targeting survivin has been reported, which may be due to its poor ability to induce cellular immunity. Thus, a suitable immunoadjuvant and optimized immunization strategy can greatly enhance the cellular immune response to this protein vaccine. DDA/MPL (monophosphoryl lipid A formulated with cationic dimethyldioctadecylammonium) has been reported to enhance the antigen uptake and presentation to T cells as an adjuvant. Meanwhile, a heterologous prime-boost strategy can enhance the cellular immunity of a protein vaccine by applying different antigen-presenting systems. Here, DDA/MPL and an adenovirus prime-protein boost strategy were applied to enhance the specific anti-tumor immunity of a truncated survivin protein vaccine. Antigen-specific IFN-γ-secreting T cells were increased by 10-fold, and cytotoxic T lympohocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Meanwhile, the Th1 type cellular immune response was strongly enhanced and tumor inhibition was significantly increased by 96% with the adenovirus/protein prime-boost strategy, compared to the protein homologous prime-boost strategy. Moreover, this adjuvanted heterologous prime-boost strategy combined with oxaliplatin could significantly enhance the efficiency of tumor growth inhibition through promoting the proliferation of splenocytes. Thus, our results provide a novel vaccine strategy for cancer therapy using an adenovirus prime-protein boost strategy in a murine melanoma model, and its combination with oxaliplatin may further enhance the anti-tumor efficacy while alleviating side effects of the drug.
authors.affiliation: National Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Wang
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Zhang
authors.forename: Chen-Lu
authors.initials: CL
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xia
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Gu
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D000077022:Survivin; D016176:T-Lymphocyte Subsets
chemical_list: D000276:Adjuvants, Immunologic; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D008050:Lipid A; D009944:Organoplatinum Compounds; D000644:Quaternary Ammonium Compounds; D000077022:Survivin; D000077150:Oxaliplatin; C015831:dimethyldioctadecylammonium; C048436:monophosphoryl lipid A
keywords: DDA/MPL; Melanoma; Oxaliplatin; Prime-boost; Survivin