Abstract
In the 197Os it was thought that the advent of monoclonal antibody technology heralded the fruition of the search for the “magic bullet” first proposed by Ehrlich in the early years of this century (Ehrlich, 1960). In practice, however, this goal has remained elusive as a range of obstacles have presented themselves and have proved very difficult to overcome. To date, there have been numerous attempts to improve the cytotoxicity of the antibody “missile” by attaching a variety of “warheads” to them, for example, cytotoxic drugs, such as adriamycin or methotrexate, toxins, such as ricin A-chain or Pseudomonas exotoxin, and radioisotopes (Pietersz and McKenzie, 1992).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bagshawe, K. D., 1989, Towards generating cytotoxic agents at cancer sites, Br. J. Cancer 60:275–281.
Bagshawe, K. D., and Sharma, S. K., 1996, Cyclosporine delays host immune response to antibody enzyme conjugate in ADEPT, Transplant. Proc. 28:3156–3158.
Bagshawe, K. D., Sharma, S. K., Springer, C. J., Antoniw, P., Boden, J. A., Rogers, G. T., Burke, P. J., Melton, R. G., and Sherwood, R. F., 1991, Antibody Directed Enzyme Prodrug Therapy (ADEPT)—clinical report, Disease Marker 9:233–238.
Begent, R. H. J., 1985, Recent advances in tumour imaging: Use of radiolabelled monoclonal antibodies, Biochim. Biophys. Acta 780:151–166.
Bosslet, K., Czech, J., and Hoffmann, D., 1994, Tumor-selective prodrug activation by fusion protein-mediated catalysis, Cancer Res. 54:2151–2159.
Campbell, D. A., Gong, B., Kochersperger, L. M., Yonkovich, S., Gallop, M. A., and Schultz, P. G., 1994, Antibody-catalyzed prodrug activation, J. Am. Chem. Soc. 116:2165–2166.
Cobb, L. M., Humphreys, J. A., and Harrison, A., 1987, The diffusion of a tumour-specific monoclonal antibody in lymphoma infiltrated spleen, Br. J. Cancer 55:53–55.
Desutter, K. and Fiers, W. A., 1994, Bifunctional murine-human chimeric antibody with one antigen-binding arm replaced by bacterial beta-lactamase. Mol. Immunol. 31:261–267.
Ehrlich, P. The Collected Papers of P. Ehrlich, Pergamon Press, London, 1960, pp. 505–518.
Fargion, S., Carney, D., Mulshine, J., Rosen, S., Bunn, P., Jewitt, P., Cuttitta, F., Gazdar, A., and Minna, J., 1986, Heterogeneity of cell surface antigen expression of human small cell lung cancer detected by monoclonal antibodies, Cancer Res. 46:2633–2638.
Frei, E. III, Teicher, B. A., Holden, S. A., Cathcart, K. N. S., and Wang, Y., 1988, Preclinical studies and clinical correlation of the effect of alkylating dose, Cancer Res. 48:6417–6423.
Goldenberg, D. M., Sharkey, R. M., Hall, T. C., Murthy, S., Siegal, J. A., Izon, D. O., Swayne, L. C., Lake, D., Hansen, H. J., and Pinsky, M., 1991, Radioimmunotherapy of B-cell lymphomas with 131I-labeled LL2 (EPB-2) monoclonal antibody, Antibody Immunoconj. Radiopharm. 4: 763–769.
Goshorn, S. C., Svensson, H. P., Kerr, D. E., Somerville, J. E., Senter, P. D., and Fell, H. P., 1993, Genetic construction, expression, and characterization of a single chain anticarcinoma antibody fused to ß-lactamase, Cancer Res. 53:2123–2127.
Haenseler, E., Esswein, A., Vitols, K. S., Montejano, Y., Mueller, B. M., Reisfeld, R. A., and Huennekens, E. M., 1992, Activation of methotrexate-alpha-alanine by carboxypeptidase-A monoclonal antibody conjugate, Biochemistry 31:891–897.
Melton, R. G., Rowland, J. A., Pietersz, G. A., Sherwood, R. E, and McKenzie, I. E C., 1993, Tumour necrosis factor increases tumour uptake of co-administered antibody-carboxypeptidase-G2 conjugate, Eur. J. Cancer 29A:1177–1183.
Melton, R. G., 1996, Preparation and purification of antibody-enzyme conjugates for therapeutic applications, Adv. Drug Delivery Rev. 22:289–301.
Meredith, R. E, Khazaeli, M. B., Pion, W. E., Liu, T., Russell, C. D., Wheeler, R. H., and Lobuglio, A. E, 1993, Effect of human immune response on repeat courses of131í-chimeric B72.3 antibody therapy, Antibody Immunoconj. Radiopharm. 6:39–46.
Moshakis, V., Mcllhinney, R. A. J., and Neville, A. M., 1981, Cellular distribution of monoclonal antibody in human tumours after I.V. administration, Br. J. Cancer 44:663–669.
Natali, P. G., Cavaliere, R., Bigotti, A., Nicotra, M. R., Russo, C., Ng, A. K., Giacomini, P., and Ferrone, S. (1983), Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions, J. Immunol. 130:1462–1466.
Neuberger, M. S., Williams, G. T., and Fox, R. 0., 1984, Recombinant antibodies possessing novel effector functions, Nature 312:604–608.
Pietersz, G. A. and McKenzie, I. F. C., 1992, Antibody conjugates for the treatment of cancer, Immunol. Rev. 129:57–80.
Rogers, G. T., Burke, P. J., Sharma, S. K., Koodie, R., and Boden, J. A., 1995, Plasma clearance of an antibody-enzyme conjugate in ADEPT by monoclonal anti-enzyme: Its effect on prodrug activation in vivo, Br. J. Cancer 72:1357–1363.
Sehon, A. H., 1991, Carl Prausnitz Memorial Lecture—Suppression of antibody responses by chemically modified antigens, Int. Arch. Allergy Appl. Immunol. 94:11–20.
Sharma, S. K., Bagshawe, K. D., Burke, P. J., Boden, J. A., Rogers, G. T, Springer, C. J., Melton, R. G., and Sherwood, R. F., 1994, Galactosylated antibodies and antibody-enzyme conjugates in antibody-directed enzyme prodrug therapy, Cancer 73:1114–1120.
Sharma, S. K., Bagshawe, K. D., Burke, P. J., Boden, J. A., and Rogers, G. T., 1990, Inactivation and clearance of an anti-CEA carboxypeptidase G2 conjugate in blood after localisation in a xenograft model, Br. J. Cancer 61:659–662.
Sharma, S. K., Bagshawe, K. D., Melton, R. G., and Begent, R. H. J., 1996, Effect of cyclosporine on immunogenicity of a bacterial enzyme carboxypeptidase G2 in ADEPT, Transplant. Proc. 28:3154–3155.
Sharma, S. K., Bagshawe, K. D., Melton, R. G., and Sherwood, R. F., 1992, Human immune response to monoclonal antibody-enzyme conjugates in ADEPT, Cell Biophys. 21:109–120.
Shepherd, T. A., Jungheim, L. N., Meyer, D. L., and Starling, J. K., 1991, A novel targeted delivery system utilizing a cephalosporin-oncolytic prodrug activated by an antibody 3-lactamase conjugate for the treatment of cancer, Bioorg. Medicinal Chem. Let. 1:21–26.
Springer, C. J., Bagshawe, K. D., Sharma, S. K., Searle, F., Boden, J. A., Antoniw, P., Burke, R J., Rogers, G. T., Sherwood, R. Y., and Melton, R. G., 1991, Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds, Eur. J. Cancer 27:1361–1366.
Stevenson, G. T. and Stevenson, E K., 1975, Antibody to a molecularly defined antigen confined to a tumour cell surface, Nature 254:714–716.
Tagliabue, E., Porro, G., Barbanti, P., Tone, G. D., Menard, S., Rilke, E, Cerasoli, S., and Colnaghi, M. I., 1986, Improvement of tumor cell detection using a pool of monoclonal antibodies, Hybridoma 5:107–115.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Knox, R.J., Melton, R.G. (1999). Introduction. In: Melton, R.G., Knox, R.J. (eds) Enzyme-Prodrug Strategies for Cancer Therapy. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4823-2_1
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4823-2_1
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7186-1
Online ISBN: 978-1-4615-4823-2
eBook Packages: Springer Book Archive