title: Fusion of Hsp70 to Mage-a1 enhances the potency of vaccine-specific immune responses.
abstract: BACKGROUND
  Heat shock proteins (HSPs) are capable of promoting antigen presentation of chaperoned peptides through interactions with receptors on antigen presenting cells. This property of HSPs suggests a potential function as an adjuvant-free carrier to stimulate immune responses against a covalently linked fusion partner. MAGE-A1 is a likely candidate for tumor immunotherapy due to its abundant immunogenic epitopes and strict tumor specificity. To analyze the influence of HSP70 conjugation to MAGE-A1, towards developing a novel effective vaccine against MAGE-expressing tumors, we cloned the murine counterpart of the human HSP70 and MAGE-A1 genes.
  
  
  METHODS
  Recombinant proteins expressing Mage-a1 (aa 118-219), Hsp70, and Mage-a1-Hsp70 fusion were purified and used to immunize C57BL/6 mice. The humoral and cellular responses elicited against Mage-a1 were measured by ELISA, IFN-γ ELISPOT assay, and cytotoxicity assay.
  
  
  RESULTS
  Immunization of mice with Mage-a1-Hsp70 fusion protein elicited significantly higher Mage-a1-specific antibody titers than immunization with either Mage-a1 alone or a combination of Mage-a1+Hsp70. The frequency of IFN-γ-producing cells and the cytotoxic T lymphocyte (CTL) activity was also elevated. Consistent with the elevated immune response, immunization with fusion protein induced potent in vivo antitumor immunity against MAGE-a1-expressing tumors.
  
  
  CONCLUSIONS
  These results indicate that the fusion of Hsp70 to Mage-a1 can enhance immune responses and anti-tumor effects against Mage-a1-expressing tumors. Fusion of HSP70 to a tumor antigen may greatly enhance the potency of protein vaccines and can potentially be applied to other cancer systems with known tumor-specific antigens. These findings provide a scientific basis for the development of a novel HSP70 and MAGE fusion protein vaccine against MAGE-expressing tumors.
authors: Department of Pathology, The First Affiliated Hospital, Guangzhou Medical University, 151, Yanjiang Road, Guangzhou 510120, China. juhongjiang2006@yahoo.com.
authors: Juhong
authors: J
authors: Jiang
authors: Dan
authors: D
authors: Xie
authors: Wenmin
authors: W
authors: Zhang
authors: Gang
authors: G
authors: Xiao
authors: Jianming
authors: J
authors: Wen
mesh_terms: D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D064166:Vaccine Potency
chemical_list: D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D009363:Neoplasm Proteins