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Development of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapy

Cancer Gene Therapy volume 15, pages 723–732 (2008)Cite this article

Abstract

The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 × 108 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 × 1011 v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 × 109 PFU) of rAdv-hTERTC27 significantly augmented the therapeutic effects and led to a 38% complete tumor regression rate. In vivo optical imaging also showed that rAAV-luc/rAdv-luc cocktail vectors could synergistically enhance the early transient and latent sustained expression of luciferase, as compared to rAdv-luc and rAAV-luc alone. These findings suggest that the combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is potentially a promising treatment for glioblastoma, and the rAAV/rAdv cocktail vector system warrants further development for cancer gene therapy.

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Acknowledgements

The work was supported by Innovation and Technology Fund (ITS/105/02 to MCL) and grants from the Hong Kong Research Grant Council (CUHK 7422/03M to HFK) and Guangzhou Metropolitan Fund (2005Z1-E0131).

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Author notes

  1. Y Gao and S S M Ng: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China

    Y Gao, S S M Ng, D H W Chau, H Yao, C Yang & M C Lin

  2. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Y Gao

  3. Joint State Key Laboratory in Oncology in South China, Sun Yat-Sen University, Guangzhou, China

    D H W Chau & H-F Kung

  4. Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    D H W Chau & H-F Kung

  5. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    K Man

  6. Department of Tumor and Molecular Biology, Beijing Institute of Biotechnology, Beijing, China

    P T Huang, C Huang & J J Huang

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  1. Y Gao
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  2. S S M Ng
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Correspondence to M C Lin.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt)

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Gao, Y., Ng, S., Chau, D. et al. Development of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapy. Cancer Gene Ther 15, 723–732 (2008). https://doi.org/10.1038/cgt.2008.33

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