DNA and Adenovirus Tumor Vaccine Targeting Truncated Survivin Generates Specific Immune Responses an

来源 :BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会) | 被引量 : 0次 | 上传用户:superrocli
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  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 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 and 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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