Antibody-directed enzyme prodrug therapy with the T268g mutant of human carboxypeptidase A1: In vitro and in vivo studies with prodrugs of methotrexate and the thymidylate synthase inhibitors GW1031 and GW1843

Bioconjugate Chemistry

Volumn 10, Issue 1, 1999, Pages 38-48

  Wolfe, L A ^a   Mullin, R J ^a   Laethem, R ^a   Blumenkopf, T A ^a   Cory, M ^a   Miller, J F ^a   Keith, B R ^a   Humphreys, J ^a   Smith, G K ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY DIRECTED ENZYME PRODRUG THERAPY; CARBOXYPEPTIDASE A1; CONJUGATE; DIHYDROFOLATE REDUCTASE INHIBITOR; DRUG STABILITY; ENZYME; ENZYMIC HYDROLYSIS; METHOTREXATE; MOUSE; THYMIDYLATE SYNTHASE INHIBITOR; TUMOR;

ANTIBODIES; ENZYME ACTIVITY; HYDROLYSIS; PLASMA STABILITY; TUMORS;

ANTIBODY-DIRECTED ENZYME PRODRUG THERAPIES; CARBOXYPEPTIDASE; ENZYMES ACTIVITY; IN-VITRO; IN-VIVO; MUTANT ENZYMES; PRODRUGS; SYNTHASE INHIBITOR; THYMIDYLATE SYNTHASE; WILD TYPES;

CHEMOTHERAPY;

EID: 0032944227     PISSN: 10431802     EISSN: None     Source Type: Journal    
DOI: 10.1021/bc980057z     Document Type: Article

References (35)

1. Zubrod, C. G. (1982) Principles of chemotherapy. in Cancer Medicine (Holland, J. F., and Frei, E., Eds.) pp 627-632, Lea & Febiger, Philadelphia.
2. Mihich, E., and Creaven, P. J. (1982) Principles of pharmacology and toxicology. in Cancer Medicine (Holland, J. F., and Frei, E., Eds.) pp 685-715, Lea & Febiger, Philadelphia.
3. Hellstrom, K. E., Hellstrom, I., and Goodman, G. E. (1987) Antibodies for drug delivery. in Controlled Drug Delivery, Fundamentals and Applications (Robinson, J. R., and Lee, V. H. L., Eds.) 2nd ed., pp 623-653, Marcel Dekker, New York.
4. Smyth, M. J., Pietersz, G. A., Classon, B. J., and McKenzie, I. F. C. (1986) Specific targeting of chlorambucil to tumors with the use of monoclonal antibodies. J. Natl. Cancer Inst. 76(3), 503-510.
5. Senter, P. D. (1990) Activation of prodrugs by antibody-enzyme conjugates: a new approach to cancer therapy. FASEB J. 4, 188-193.
6. Bagshawe, K. D., Springer, C. J., Searle, F., Antoniw, P., Sharma, S, K., Melton, R. G., and Sherwood, R. F. (1988) A cytotoxic agent can be generated selectively at cancer sites. Br. J. Cancer 58, 700-703.
7. Bagshawe, K. D. (1989) Towards generating cytotoxic agents at cancer sites. Br. J. Cancer 60, 275-281.
8. Hellstrom, K. E., and Senter, P. D. (1991) Activation of prodrugs by targeted enzymes. Eur. J. Cancer 27(11), 1342-1343.
9. Philpott, G. W., Bower, R. J., Parker, K. L., Shearer, W. T., and Parker, C. W. (1974) Affinity cytotoxicity of tumor cells with antibody-glucose oxidase conjugates, peroxidase, and arsphenamine. Cancer Res. 34, 2159-2164.
10. Philpott, G. W., Bower, R. J., and Parker, C. (1973) Selective iodination and cytotoxicity of tumor cells with an antibody-enzyme conjugate. Surgery (St. Louis) 74(1), 51-58.
11. Senter, P. D., Wallace, P. M., Svensson, H. P., Kerr, D. E., Hellstrom, I., and Hellstrom, K. E. (1991) Activation of prodrugs by antibody-enzyme conjugates. in Immunobiology of proteins and peptides VI (Atassi, M. Z., Ed.) pp 97-105, Plenum Press, New York.
12. Wallace, P. M., and Senter, P. D. (1991) In vitro and in vivo activities of monoclonal antibody-alkaline phosphatase conjugates in combination with phenol mustard phosphate. Bioconjugate Chem. 2(5), 349-352.
13. Haisma, H. J., Boven, E., van Muijen, M., De Vries, R., and Pinedo, H. M. (1992) Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline phosphatase for specific activation of the prodrug etoposide phosphate. Cancer Immunol. Immunother. 34, 343-348.
14. Senter, P. D., Schreiber, G. J., Hirschberg, D. L., Ashe, S. A., Hellstrom, K. E., and Hellstrom, I. (1989) Enhancement of the in vitro and in vivo antitumor activities of phosphorylated mitomycin C and etoposide derivatives by monoclonal antibody-alkaline phosphatase conjugates. Cancer Res. 49, 5789-5792.
15. Senter, P. D., Saulnier, M. G., Schreiber, G. J., Hirschberg, D. L., Brown, J. P., Hellstrom, I., and Hellstrom, K. E., (1988) Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. Proc. Natl. Acad. Sci. U.S.A. 85, 4842-4846.
16. Haenseler, E., Esswein, A., Vitols, K. S., Montejano, Y., Mueller, B. M., Reisfeld, R. A., and Huennekens, F. M. (1992) Activation of methotrexate-α-alanine by carboxypeptidase A-monoclonal antibody conjugate. Biochemistry 31, 891-897.
17. Senter, P. D., Su, P. C. D., Katsuragi, T., Sakai, T., Cosand, W. L., Hellstrom, I., and Hellstrom, K. E., (1991) Generation of 5-fluorouracil from 5-fluorocytosine by monoclonal antibody-cytosine deaminase conjugates. Bioconjugate Chem. 2, 447-451.
18. Springer, C. J., Bagshawe, K. D., Sharma, S. K., Searle, F., Boden, J., Antoniw, P., et al. (1991) Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds. Eur. J. Cancer 27(11), 1361-1366.
19. Smith, G. K., Banks, S., Blumenkopf, T. A., Cory, M., Humphreys, J., Laethem, R. M., Miller, J., Moxham, C. P., Mullin, R., Ray, P. H., Walton, L. M., and Wolfe, L. A. (1997) Toward Antibody-directed enzyme prodrug therapy with the T268G mutant of human carboxypeptidase A1 and novel in vivo stable prodrugs of MTX. J. Biol. Chem. 272(25), 15804-15816.
20. Pendergast, W., Dickeerson, S. H., Dev, I. K., Ferone, R., Duch, D. S., and Smith, G. K. (1994) Benzo[f]quinazoline inhibitors of thymidylate synthase: Methyleneamino-linked aroylglutamate derivitives. J. Med. Chem. 37(6), 838-844.
21. Duch, D. S., Banks, S., Dev, I. K., Dickerson, S. H., Ferone, R., Heath, L. S., Humphreys, J., Knick, V., Pendergast, W., Singer, S., Smith, G. K., Waters, K., and Wilson, H. R. (1993) Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase. Cancer Res. 53, 810-818.
22. Smith, G. K., Amyx, H., Boytos, C. M., Duch, D. S., Ferone, R., and Wilson, H. R. (1995) Enhanced antitumor activity for the thymidylate synthase inhibitor for 1843U89 through decreased host toxicity with oral folic acid. Cancer Res. 55, 6117-6125.
23. Pendergast, W., Dickerson, S., Dev, I., Ferone, R., Duch, D., and Smith, G. (1992) Benzoquinazoline inhibitors of thymidylate synthase: effect on cytotoxicity and thymidylate synthase activity of variation of side chain structure and C3 substitution. Proc. Am. Assoc. Cancer Res. 33, 407.
24. Banks, S. D., Waters, K. A., Barrett, L. L., and Smith, G. K. (1992) Destruction of WiDr multicellular tumor spheroids with novel thymidylate synthase inhibitor at physiological thymidine concentrations. Proc. Am. Assoc. Cancer Res. 33, 407.
25. Wilson, H. R., Heath, L. S., Knick, V. C., Koszalka, G. W., and Ferone, R. (1992) In vivo antitumor activity of GW1843, a new antifolate thymidylate synthase inhibitor. Proc. Am. Assoc. Cancer Res. 33, 407.
26. Vitols, K. s., Haag-Zeino, B., Baer, T., Montejano, Y. D., and Huennekens, F. M. (1995) Methotrexate-α-phenylalanine: Optimization of methotrexate prodrug for activation by carboxypeptidase A-monoclonal antibody conjugate. Cancer Res. 55, 478-481.
27. Rosenberg, I. H., and Selhub, J. (1986) Intestinal Absorption of Folates. in Folates and Pterins (Blakley, R. L., and Whitehead, V. M., Eds.) Vol. 3, pp 148-176, Wiley-Interscience, New York.
28. Lituinov, S. V., Velders, M. P., Bakker, H. A., Fleuren, G. J., and Warnaar, S. O. (1994) Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J. Cell Biol. 125(2), 437-446.
29. Kidera, A., Inaka, K., Matsushima, M., Go, N. (1994) Response of dynamic structure to removal of a disulfide bond: normal mode refinement of C77A/C95A mutant of human lysozyme. Protein Sci. 3 (1), 92-102.
30. Gardell, S. J., Craik, C. S., Clauser, E., Goldsmith, E. J., Stewart, C. B., Graf, M., and Rutter, W. J. (1988) A novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family. J. Biol. Chem. 263(33), 17828-17836.
31. Laethem, R. M., Blumenkopf, T. A., Cory, M., Elwell, L., Moxham, C. P., Ray, P. H., Walton, L. M., and Smith, G. (1996) Expression and characterization of human pancreatic preprocarboxypeptidase A1 and preprocarboxypeptidase A2. Arch. Biochem. Biophys. 332, 8-18.
32. Cueni, L. B., Bazzone, T. J., Riordan, J. F., and Vallee, B. L. (1980) Affinity chromatographic sorting of carboxypeptidase A and its chemically modified derivatives. Anal. Biochem. 107, 341-349.
33. Vitols, K. S., Hanseler, E., Montejano, Y., Muller, B. M., Reisfeld, R. A., and Huennekens, F. M. (1992) Enhanced cytotoxicity of methotrexate alpha-peptide prodrugs for UCLA-P3 cells treated with enzyme-conjugated monoclonal antibody KS1/4. Antibody, Immunoconjugates, Radiopharm. 5(1), 140.
34. Sirotnak, F. M., DeGraw, J. I. (1984) Selective antitumor action of folate analogues. in Folate Antagonist as Therapeutic Agents (Sirotnak, F. M., Burchall, J. J., Ensminger, W. B., and Montgomery, J. A., Eds.) Vol 2, pp 47-54, Academic Press, Inc., Orlando.
35. Jackman, A. L., Taylor, G. A., Calvert, A. H., and Harrap, K. R. (1984) Modulation of anti-metabolite effects: Effects of thymidine on the efficacy of the quinazoline-based thymidylate synthetase inhibitor, CB3717. Biochem. Pharmacol. 33, 3269-3275.