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Adeno-associated virus mediated gene transfer into lung cancer cells promoting CD40 ligand-based immunotherapy

南京医科大学学报(自然科学版) 2008年第1期 116-116页

作者： Wu,J. Q. Zhao,W. H. Li,Y. Zhu,b. Yin,K. S. Nanjing Med Univ,Affiliated Hosp 1,Nanjing 210029,Jiangsu,Peoples R China.

Expression of the CD40 ligand(CD40L) on tumors can activate host immune systems and produce antitumor effects against the tumors. To deliver the CD40L gene efficiently,we evaluated the efficiency of transduction of different serotypes of adeno-associated virus(AAV) vectors in lung cancer A549 cells and compared the transduction efficiency of a conventional AAV vector with that of self-complementary AAV(scAAV) vectors as well. We determined that serotype AAV2/5 transduced A549 cells much more efficiently than serotypes AAV2/1,AAV2/2,AAV2/6,AAV2/7,AAV2/8,AAV2/9 and AAV2/10. And the transduction efficiency of scAAV2/5 was significantly higher than conventional AAV2/5. Furthermore,pretreatment with carboplatin,which is a chemotherapeutic agent used in lung cancer chemotherapy,substantially increased AAV-mediated transgene expression. The scAAV2/5 vectors encoding human CD40L were used to tranduce CD40L into A549 cells,which were then co-cultivated with immature human dendritic cells(DCs). Interleukin 12(IL-12) that was released was measured in the culture supernatant. Specificity of the immunostimulatory effect of CD40L was confirmed by blocking with a monoclonal antibody binding to human CD40L. The in vivo antitumor activity was evaluated in bALb/c nude mice hearing A549 lung cancer. scAAV2/5-CD40L showed significant inhibitory effects on the growth of transplanted tumor cells as compared with control group. These studies suggest that recombinant AAV2/5-CD40L may provide an effective form of therapy for lung cancer. (c)2007 Elsevier Inc. All rights reserved.

关键词： adeno-associated virus serotype transduction efficiency lung neoplasms CD40 ligand(CD40L) dendritic cells vectors in-vitro efficient transduction transgene expression cystic-fibrosis dendritic cells hemophilia-b factor-ix t-cells phase-i therapy

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