The treatment and prevention of mouse melanoma with an oral DNA vaccine carried by attenuated Salmonella typhimurium.
Therapeutic vaccines of cancer are attractive for their capacity of breaking the immune tolerance and invoking long-term immune response targeting cancer cells without autoimmunity. An efficient antigen delivery system is the key issue of developing an effective cancer vaccine. Attenuated Salmonella typhimurium as the carrier of cancer vaccine are able to transfer DNA from the prokaryote to the eukaryote and preferentially replicate within the tumor tissue. Heat shock protein 70 delivers the tumor-associated antigens to antigen presenting cells through its polypeptide-binding domain and breaks immune tolerance of the cancer cells. Here we described a novel low-copy-number DNA vaccine based on the Hsp70-TAA complex and carried by the attenuated S. typhimurium strain SL3261. Oral administration of this vaccine elicited specific CTL-mediated lysis of the melanoma tumor cells and marked activation of the T-cells. The therapeutic vaccine effectively protected 57.1% C57BL/6J mice from lethal challenge with B16F10 melanoma tumor cells in prophylactic settings and eraicated 62.5% tumor growth in therapeutic settings. This approach may provide a new strategy for the prevention and treatment of cancer.
Zhu
Xiangying
X
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai 200433, PR of China.
Cai
Jianguo
J
Huang
Jiajie
J
Jiang
Xinyin
X
Ren
Daming
D
D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics; D019496:Cancer Vaccines; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics; D007167:Immunotherapy; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA / Q000235:genetics / Q000382:microbiology / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase