Heat shock protein 70 / MAGE-1 tumor vaccine can enhance the potency of MAGE-1-specific cellular immune responses in vivo.
The cancer-testis antigen encoded by the MAGE-1 gene is an attractive antigen in tumor immunotherapy because it can be processed as a foreign antigen by the immune system and generate tumor-specific cellular immune response in vivo. However, increase of the potency of MAGE-1 DNA vaccines is still needed. The high degree of sequence homology and intrinsic immunogenicity of heat shock protein 70 (HSP70) have prompted the suggestion that HSP70 might have immunotherapeutic potential, as HSP70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen-presenting cells to elicit peptide-specific immunity. In this research, we evaluated the enhancement of linkage of Mycobacterium tuberculosis HSP70 to MAGE-1 gene of the potency of antigen-specific immunity elicited by naked DNA vaccines. We found that vaccines containing MAGE-1-HSP70 fusion genes enhanced the frequency of MAGE-1-specific cytotoxic T cells in contract to vaccines containing the MAGE-1 gene alone. More importantly, the fusion converted a less effective DNA vaccine into one with significant potency against established MAGE-1-expressing tumors. These results indicate that linkage of HSP70 to MAGE-1 gene may greatly enhance the potency of DNA vaccines, and generate specific antitumor immunity against MAGE-1-expressing tumors.
Ye
Jing
J
Laboratory of Cancer Immunology and Immunotherapy, Department of Pathology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Chen
Guang-Sheng
GS
Song
Hong-Ping
HP
Li
Zeng-Shan
ZS
Huang
Ya-Yu
YY
Qu
Ping
P
Sun
Yu-Jing
YJ
Zhang
Xiu-Min
XM
Sui
Yan-Fang
YF
D000818:Animals; D000938:Antigen-Presenting Cells; D000951:Antigens, Neoplasm; D019677:Artificial Gene Fusion; D019496:Cancer Vaccines / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; C072011:MAGEA1 protein, human; C489518:Mageb1 protein, mouse; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D019444:Vaccines, DNA