Cell Biophysics

, Volume 24, Issue 1–3, pp 83–91 | Cite as

ADEPT and related concepts

  • K. D. Bagshawe


Antibody-based therapy has attracted interest because of its potential to improve selectivity. But the limitations of antibodies as delivery systems are well known and the objective of restricting action to tumor sites requires additional means. The ADEPT concept introduced two components, enzyme and prodrug, that have the advantage that they can be secondarily manipulated to augment the selectivity of the primary delivery systems.

An antibody-enzyme conjugate (AEC) is no more selective as a delivery system than antibody itself and total catalytic capacity in tumor, plasma, and nontumor tissues is a function not only of concentration but also of volume. It is pointless giving a prodrug that is promptly activated by enzyme in blood. The ability to inactivate or clear plasma enzyme (PENCIL) by an antibody directed at its active site and modified to have low potential to penetrate the tumor is one of several ways of improving partition of enzyme between tumor and nontumor.

A second opportunity for manipulation arises from structural differences between prodrug and active drug and the potential of enzymes to exploit that difference. However effective the enzyme delivery system, some leakage of active drug into plasma is likely and active drug access to hemopoietic tissues is dose limiting. An enzyme for which the active drug, but not the prodrug, is substrate, and which is conjugated to a macromolecule, is proposed. Some thymidylate synthetase inhibitors suggest themselves as ready agents for use in this intravascular inactivation of active drug (IVIAD). This approach is an alternative to inactivation of plasma enzyme.


Folinic Acid Rescue Agent Nontumor Tissue Cell Biophysics Volume Plasma Enzyme 
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  1. 1.
    Bagshawe, K. D. (1987)Br. J. Cancer 56, 531–532.PubMedGoogle Scholar
  2. 2.
    Bagshawe, K. D., Springer, C. J., Searle, F., Antoniw, P., Sharma, S. K., Melton, R. G., et al. (1988)Br. J. Cancer 58, 700–703.PubMedGoogle Scholar
  3. 3.
    Bagshawe, K. D. (1989)Br. J. Cancer 60, 275–281.PubMedGoogle Scholar
  4. 4.
    Senter, P. D., Saulnier, M. G., Schreiber, G. J., Hirschberg, D. L., Brown, J. P., Hellstrom, I., et al. (1988)Proc. Natl. Acad. Sci. USA 85, 4842–4846.PubMedCrossRefGoogle Scholar
  5. 5.
    Sharma, S. K., Bagshawe, K. D., Burke, P. J., Boden, R. W., and Rogers, G. T. (1990)Br. J. Cancer 61, 659–662.PubMedGoogle Scholar
  6. 6.
    Sharma, S. K., Bagshawe, K. D., Searle, F., Melton, R. G., Rogers, G. T., Boden, J. A., et al. (1991)Disease Markers 9, 225–231.PubMedGoogle Scholar
  7. 7.
    Sharma, S. K., Bagshawe, K. D., Burke, P. J., Boden, J. A., Rogers, G. T., Springer, C. J., et al. (1993)Cancer in press.Google Scholar
  8. 8.
    Huennekins, F. M., Kuefner, U., Esswein, A., Fan, J., Montejano, Y., and Vitols, K. S. (1990)Chemistry and Biology of Pteridines, Walter de Gruyter, New York.Google Scholar
  9. 9.
    Sherwood, R. F., Melton, R. G., Alwan, S. M., and Hughes, P. (1985)Eur. J. Biochem. 148, 447–453.PubMedCrossRefGoogle Scholar
  10. 10.
    Philpott, G. W., Bower, R. J., and Parker, C. W. (1973)Surgery 74, 51–58.PubMedGoogle Scholar
  11. 11.
    Bertino, J. R., O'Brien, P., and McCullough, J. L. (1971)Science 172, 161–172.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • K. D. Bagshawe
    • 1
  1. 1.Charing Cross and Westminster Medical SchoolLondonUK

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