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Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity

  作者 Osada, T; Yang, XY; Hartman, ZC; Glass, O; Hodges, BL; Niedzwiecki, D; Morse, MA; Lyerly, HK; Amalfitano, A; Clay, TM  
  选自 期刊  Cancer gene therapy;  卷期  2009年16-9;  页码  673-682  
  关联知识点  
 

[摘要]Recombinant serotype 5 adenovirus (Ad5) vectors lacking E1 expression induce robust immune responses against encoded transgenes in pre-clinical models, but have muted responses in human trials because of widespread pre-existing anti-adenovirus immunity. Attempts to circumvent Ad5-specific immunity by using alternative serotypes or modifying capsid components have not yielded profound clinical improvement. To address this issue, we explored a novel alternative strategy, specifically reducing the expression of structural Ad5 genes by creating E1 and E2b deleted recombinant Ad5 vectors. Our data show that [E1-, E2b-] vectors retaining the Ad5 serotype are potent immunogens in pre-clinical models despite the presence of significant Ad5-specific immunity, in contrast to [E1-] vectors. These pre-clinical studies with E1 and E2b- deleted recombinant Ad5 vectors suggest that anti-Ad immunity will no longer be a limiting factor, and that clinical trials to evaluate their performance are warranted. Cancer Gene Therapy (2009) 16, 673-682; doi:10.1038/cgt.2009.17; published online 20 February 2009

 
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