MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model.
MUC1 and survivin are ideal tumor antigens. Although many cancer vaccines targeting survivin or MUC1 have entered clinical trials, no vaccine combining MUC1 and survivin have been reported. Due to tumor heterogeneity, vaccines containing a combination of antigens may have improved efficacy and coverage of a broader spectrum of cancer targets. Here, cellular responses and anti-tumor activities induced by a combination of DNA vaccine targeting MUC1 and survivin (MS) were evaluated. Results showed that CTL activity and inhibition of tumor growth were obviously enhanced in mice immunized with the combined vaccine in a protection assay. However, in order to enhance the therapeutic effect in the treatment assay, a recombinant adenovirus (rAd) vaccine expressing MUC1 and survivin (Ad-MS) was used as a booster following the DNA vaccine prime. Meanwhile, IL-2 promoting T cell proliferation was used as an immunoadjuvant for the DNA vaccine. Results showed that the CTL activity response to the DNA vaccine was enhanced nearly 200% when boosted by the rAd vaccine and was further enhanced by nearly 60% when combined with the IL-2 adjuvant. Therefore, DNA prime combined with rAd boost and IL-2 (MS/IL2/Ad-MS) adjuvant was considered as the best strategy and further evaluated. Multiple cytokines promoting cellular immune responses were shown to be greatly enhanced in mice immunized with MS/IL2/Ad-MS. Moreover, in the treatment assay, the tumor inhibition rate of MS/IL2/Ad-MS reached up to 50.1%, which may be attributed to the enhancement of immune responses and reduction of immunosuppressive factors in tumor-bearing mice. These results suggested that immunization with the combination vaccine targeting MUC1 and survivin using a DNA prime-rAd boost strategy along with IL-2 adjuvant may be an effective method for breaking through immune tolerance to tumors expressing these antigens with potential therapeutic benefits in melanoma cancer.
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Haihong
H
Zhang
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Chenlu
C
Liu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Fangfang
F
Zhang
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Fei
F
Geng
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Qiu
Q
Xia
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Zhenzhen
Z
Lu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Ping
P
Xu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Yu
Y
Xie
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Hui
H
Wu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Bin
B
Yu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
Jiaxin
J
Wu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China. Electronic address: xianghui@jlu.edu.cn.
Xianghui
X
Yu
National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China. Electronic address: weikong@jlu.edu.cn.
Wei
W
Kong
D000256:Adenoviridae; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D007376:Interleukin-2 / Q000008:administration & dosage; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D017778:Vaccines, Combined / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2; C060192:MUC1 protein, human; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D017778:Vaccines, Combined; D019444:Vaccines, DNA
Cancer vaccine; DNA prime–rAd boost; IL-2 adjuvant; MUC1; Survivin