DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model.
Survivin is overexpressed in major types of cancer and is considered an ideal "universal" tumor-associated antigen that can be targeted by immunotherapeutic vaccines. However, its anti-apoptosis function raises certain safety concerns. Here, a new truncated human survivin, devoid of the anti-apoptosis function, was generated as a candidate tumor vaccine. Interleukin 2 (IL-2) has been widely used as an adjuvant for vaccination against various diseases. Meanwhile, the DNA prime and recombinant adenovirus (rAd) boost heterologous immunization strategy has been proven to be highly effective in enhancing immune responses. Therefore, the efficacy of a new cancer vaccine based on a truncated form of survivin, combined with IL-2, DNA prime, and rAd boost, was tested. As prophylaxis, immunization with the DNA vaccine alone resulted in a weak immune response and modest anti-tumor effect, whereas the tumor inhibition ratio with the DNA vaccine administered with IL-2 increased to 89 % and was further increased to nearly 100 % by rAd boosting. Moreover, complete tumor rejection was observed in 5 of 15 mice. Efficacy of the vaccine administered therapeutically was enhanced by nearly 300 % when combined with carboplatin. These results indicated that vaccination with a truncated survivin vaccine using DNA prime-rAd boost combined with IL-2 adjuvant and carboplatin represents an attractive strategy to overcoming immune tolerance to tumors and has 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. zhanghh@jlu.edu.cn
Haihong
H
Zhang
Yuqian
Y
Wang
Chenlu
C
Liu
Lixing
L
Zhang
Qiu
Q
Xia
Yong
Y
Zhang
Jiaxin
J
Wu
Chunlai
C
Jiang
Yan
Y
Chen
Yongge
Y
Wu
Xiao
X
Zha
Xianghui
X
Yu
Wei
W
Kong
D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000077022:Survivin; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; C508594:IL2 protein, human; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2; D000077022:Survivin; D019444:Vaccines, DNA; D016190:Carboplatin