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Stable antibody expression at therapeutic levels using the 2A peptide

Nature Biotechnologyvolume 23pages584590 (2005) | Download Citation

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Abstract

Therapeutic monoclonal antibodies (mAbs) are currently being developed for the treatment of cancer and other diseases. Despite clinical success, widespread application of mAb therapies may be limited by manufacturing capabilities. In this paper, we describe a mAb delivery system that allows continuous production of a full-length antibody at high-concentrations in vivo after gene transfer. The mAb is expressed from a single open reading frame by linking the heavy and light chains with a 2A self-processing peptide derived from the foot-and-mouth disease virus. Using this expression system, we generated a recombinant adeno-associated virus vector encoding the VEGFR2-neutralizing mAb DC101 (rAAV8-DC101). A single dose of rAAV8-DC101 resulted in long-term expression of >1,000 μg/ml of DC101 in mice, demonstrating significant anti-tumor efficacy. This report describes the first feasible gene therapy approach for stable delivery of mAbs at therapeutic levels, which may serve as an attractive alternative to direct injection of mAbs.

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Acknowledgements

The authors would like to thank Mingxia Shi, Sandra Sanchez, Lei Xu, Gail Colbern and the animal service group of Cell Genesys for technical assistance, John Leszyk at the University of Massachusetts Medical School for carrying out mass spectrometry analysis and Peter Working for critical reading of the manuscript.

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  1. Department of Preclinical Oncology and Immunology, Cell Genesys, Inc., 500 Forbes Blvd., S. San Francisco, 94080, California, USA

    • Jianmin Fang
    • , Jing-Jing Qian
    • , Saili Yi
    • , Thomas C Harding
    • , Guang Huan Tu
    • , Melinda VanRoey
    •  & Karin Jooss

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The authors are employed by Cell Genesys, Inc.

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Correspondence to Jianmin Fang.

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https://doi.org/10.1038/nbt1087

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