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A cell surface tethered enzyme improves efficiency in gene-directed enzyme prodrug therapy

Nature Biotechnology volume 15, pages 1373–1377 (1997)Cite this article

Abstract

The potential for expressing the bacterial enzyme carboxypeptidase G2 (CPG2) tethered to the outer surface of mammalian cells was examined for use in gene-directed enzyme prodrug therapy. The affinity of CPG2 for the substrate methotrexate was unaffected by three mutations required to prevent N-linked glycosylation. Breast carcinoma MDA MB 361 cells expressing CPG2 internally showed only a very modest increase in sensitivity to the prodrug CMDA because the prodrug did not enter the cells. Cells expressing surface-tethered CPG2, however, became 16–24-fold more sensitive to CMDA and could mount a good bystander effect. Systemic administration of CMDA to mice bearing established xenografts of the transfected cells led to sustained tumor regressions or cures.

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Author notes

  1. Caroline J. Springer: e-mail: caroline@icr.ac.uk.

Authors and Affiliations

  1. CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Rd., London, SW3 6JB, UK

    Richard Marais, Robert A. Spooner & Yvonne Light

  2. CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Cotswold Rd., Sutton, Surrey, SM2 5NG, UK

    Robert A. Spooner, Stephen M. Stribbling, Janet Martin & Caroline J. Springer

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  1. Richard Marais
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  2. Robert A. Spooner
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  4. Yvonne Light
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  6. Caroline J. Springer
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Marais, R., Spooner, R., Stribbling, S. et al. A cell surface tethered enzyme improves efficiency in gene-directed enzyme prodrug therapy. Nat Biotechnol 15, 1373–1377 (1997). https://doi.org/10.1038/nbt1297-1373

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  • DOI: https://doi.org/10.1038/nbt1297-1373

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