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DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model

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机构: [1]National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China [2]Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China [3]Sichuan Tumor Hospital and Institute, Chengdu 610041, China
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关键词: Survivin Tumor vaccine Prime-boost Immunoadjuvant Chemotherapeutics

摘要:
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.

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基金编号: 200903255 201103179

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出版当年[2012]版:
大类 | 2 区 医学
小类 | 3 区 免疫学 3 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 3 区 免疫学 3 区 肿瘤学
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出版当年[2012]版:
Q2 ONCOLOGY Q2 IMMUNOLOGY
最新[2023]版:
Q1 ONCOLOGY Q2 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2012版] 出版当年五年平均 出版前一年[2011版] 出版后一年[2013版]

第一作者:
第一作者机构: [1]National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China [2]Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China
通讯作者:
通讯机构: [1]National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China [2]Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China
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