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In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies

Gene Therapy volume 12, pages 988–998 (2005)Cite this article

Abstract

Lentiviral-based vectors hold great promise as gene delivery vehicles for the treatment of a wide variety of diseases. We have previously reported the development of a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), which is able to efficiently transduce dividing and nondividing cells both in vitro and in vivo. Here, we report on the application of EIAV vectors for the systemic delivery of an antibody fusion protein designed for the treatment of cancer. The therapeutic potential of a single chain antibody against the tumour-associated antigen, 5T4, fused to immune enhancer moieties has been demonstrated in vitro and here we evaluate the genetic delivery of a 5T4 scFv fused to B7.1 (scFvB7) using an EIAV vector. The kinetics and concentration of protein produced following both intravenous (i.v.) and intramuscular (i.m.) administration was determined in immune competent adult mice. In addition, the immune response to the EIAV vector and the transgene were determined. Here, we show that a single injection of EIAV expressing scFv-B7 can give rise to concentrations of protein in the range of 1–5 μg/ml that persist in the sera for more than 50 days. After a second injection, concentrations of scFv-B7.1 rose as high as 20 μg/ml and levels greater than 2 μg/ml were present in the sera of all mice injected i.v. after 210 days despite the detection of antibodies against both the transgene and viral envelope for the duration of this study. These results demonstrate the potential of EIAV as a gene therapy vector for long-term production of therapeutic recombinant proteins.

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Acknowledgements

We gratefully acknowledge MG Ryan, N Drury, A Warner and P Henbest for technical assistance.

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Author notes

  1. A Lamikanra

    Present address: Blood Research Laboratory, Nuffield Department of Clinical, Laboratory Science, John Radcliffe Hospital, Oxford, OX3 9DU, UK

  2. M W Carroll

    Present address: Molecular Nature Limited, 12 Craufurd Rise, Maidenhead, Berkshire, SL6 7LS, UK

Authors and Affiliations

  1. Oxford BioMedica, Medawar Building, Robert Robinson Avenue, Oxford Science Park, Oxford, UK

    A Lamikanra, K A Myers, K A Mitrophanous & M W Carroll

  2. Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey, UK

    N Ferris

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  1. A Lamikanra
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Lamikanra, A., Myers, K., Ferris, N. et al. In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies. Gene Ther 12, 988–998 (2005). https://doi.org/10.1038/sj.gt.3302484

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