title: Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2.
abstract: BACKGROUND
  A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2.
  
  
  METHODS
  The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated.
  
  
  RESULTS
  The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma.
  
  
  CONCLUSIONS
  Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.
authors: Meng
authors: M
authors: Li
authors: Huashan
authors: H
authors: Shi
authors: Yandong
authors: Y
authors: Mu
authors: Zichao
authors: Z
authors: Luo
authors: Hailong
authors: H
authors: Zhang
authors: Yang
authors: Y
authors: Wan
authors: Dongmei
authors: D
authors: Zhang
authors: Lian
authors: L
authors: Lu
authors: Ke
authors: K
authors: Men
authors: Yaomei
authors: Y
authors: Tian
authors: Xiaozhe
authors: X
authors: Wu
authors: Xiaoyan
authors: X
authors: Liu
authors: Ying
authors: Y
authors: Pan
authors: Yingzi
authors: Y
authors: Fan
authors: Chaoheng
authors: C
authors: Yu
authors: Bailing
authors: B
authors: Zhou
authors: Rong
authors: R
authors: Xiang
authors: State Key Laboratory of Biotherapy / Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, PR China. chenwcrs@126.com.
authors: Xiancheng
authors: X
authors: Chen
authors: Li
authors: L
authors: Yang
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000097:blood; D045142:Cross-Priming / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018925:Chemokines; D016328:NF-kappa B; C000598172:NY-ESO-1-APH vaccine; D011134:Polysaccharides