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Infectivity enhancement for adenoviral transduction of canine osteosarcoma cells

Gene Therapy volume 13, pages 389–399 (2006)Cite this article

Abstract

The full realization of conditionally replicative adenoviruses (CRAds) for cancer therapy has been hampered by the limited knowledge of CRAd function in vivo and particularly in an immunocompetent host. To address this issue, we previously proposed a canine adenovirus type 2 (CAV2)-based CRAd for clinical evaluation in canine patients with osteosarcoma (OS). In this study, we evaluated infectivity-enhancement strategies to establish the foundation for designing a potent CAV2 CRAd with effective transduction capacity in dog osteosarcoma cells. The results indicate that the native CAV2 fiber–knob can mediate increased binding, and consequently gene transfer, in both canine osteosarcoma immortalized and primary cell lines relative to previously reported Ad5 infectivity-enhancement strategies. Gene delivery was further enhanced by incorporating a polylysine polypeptide onto the carboxy terminus of the CAV2 knob. This vector demonstrated improved gene delivery in osteosarcoma xenograft tumors. These data provide the rationale for generation of infectivity-enhanced syngeneic CAV2 CRAds for clinical evaluation in a dog osteosarcoma model.

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Acknowledgements

This work was supported with grants from the NIH (P30 AR41031, RO1 CA93796, RO1 CA940840, 1P50 CA83591), Department of Defense #W81XWH-04-1-0025, the Haley's Hope Memorial Support Fund for Osteosarcoma Research, and the University of Alabama at Birmingham Medical Scientist Training Program.

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  1. L P Le and A A Rivera: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA

    L P Le, A A Rivera, J N Glasgow, V V Ternovoi, H Wu, M Wang, G P Siegal & D T Curiel

  2. Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    B F Smith

  3. Departments of Pathology, Cell Biology and Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    G P Siegal

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  1. L P Le
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Correspondence to D T Curiel.

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Le, L., Rivera, A., Glasgow, J. et al. Infectivity enhancement for adenoviral transduction of canine osteosarcoma cells. Gene Ther 13, 389–399 (2006). https://doi.org/10.1038/sj.gt.3302674

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