Induction of protective and therapeutic antitumour immunity using a novel tumour-associated antigen-specific DNA vaccine.
DNA vaccination has become an attractive immunization strategy against cancer. However, a major problem of DNA vaccination is its limited potency to be taken up by the antigen-presenting cells. In contrast, loss of immunogenic epitopes of tumour cells has urged the development of vaccines against multiple epitopes. In this study, we developed a novel strategy for the APC to efficiently cross-present a fusion tumour antigen, which contains both MHC class I-restricted and class II-restricted T-cell epitopes from Her-2/neu and p53 in a cognate manner. The N-terminus of the fusion Her-2/neu, p53 protein was linked to the sequence encoding for human secondary lymphoid-tissue chemokine for secretion and chemokinesis, and the C-terminus of the fusion protein was linked to a cell-binding domain of IgG (Fc portion, the cell-binding domain of IgG) for receptor-mediated internalization. Here, we show that the introduction of fused-gene DNA vaccine by gene gun reduced the size of established tumours and prolonged the lifespan of tumour-bearing mice. Results show that this DNA vaccination strategy can broadly enhance the antigen-specific cellular and humoral immune responses. This vaccine is capable of inducing adaptive immunity and may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.
Sun
Wenxin
W
State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences and Peking Union Medical Coillege, Beijing, China.
Qian
Haili
H
Zhang
Xueyan
X
Zhou
Chunxia
C
Liang
Xiao
X
Wang
Dongmei
D
Fu
Ming
M
Ma
Wenbo
W
Zhang
Shuren
S
Lin
Chen
C
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019677:Artificial Gene Fusion; D019470:Biolistics; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D054421:Chemokine CCL21; D019742:Chemokines, CC; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA; C515478:CCL21 protein, human; C515479:Ccl21c protein, mouse