Engineering folate-drug conjugates to target cancer: From chemistry to clinic

Bioconjugate Chemistry

Volumn 23, Issue 7, 2012, Pages 1357-1369

  Vlahov, Iontcho R ^a   Leamon, Christopher P ^a  

^a Endocyte Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MEMBRANES; CHEMOTHERAPY; CONTROLLED DRUG DELIVERY; MOLECULES; TARGETED DRUG DELIVERY;

BIOLOGICAL TARGETS; EXTRACELLULAR; FOLATE RECEPTOR; FOLATE-DRUG CONJUGATES; FOLATES; HIGH AFFINITY; HUMAN CANCER; MEMBRANE PROTEINS; PHYSIOLOGICAL SYSTEMS; PROTEIN BINDS;

DISEASES;

ALBUMIN; ANTINEOPLASTIC AGENT; CARBOPLATIN; CYSTEINE; DITHIOTHREITOL; DOXORUBICIN; EC 0225; EC 0489; EC 145; EC 193; FOLATE RECEPTOR; FOLIC ACID DERIVATIVE; GLUTATHIONE; HISTONE DEACETYLASE INHIBITOR; HOMOCYSTEINE; MITOMYCIN C; PACLITAXEL; UNCLASSIFIED DRUG; VINTAFOLIDE;

BIOENGINEERING; CELL MEMBRANE; CELL POPULATION; DISULFIDE BOND; DRUG CONJUGATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG RELEASE; DRUG SAFETY; HUMAN; HUMAN CELL; HYDROPHILICITY; IC 50; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; NONHUMAN; OVARY CANCER; PH; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; TISSUE DEGENERATION; TUMOR CELL; TUMOR XENOGRAFT; WEIGHT REDUCTION;

EID: 84863946983     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/bc2005522     Document Type: Review

References (54)

1. Oldham, R. K. and Dillman, R. O. (2008) Monoclonal antibodies in cancer therapy: 25 years of progress J. Clin. Oncol. 26, 1774-7
2. Younes, A., Bartlett, N. L., Leonard, J. P., Kennedy, D. A., Lynch, C. M., Sievers, E. L., and Forero-Torres, A. (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas New Engl. J. Med. 363, 1812-1821
3. Leamon, C. P. (2008) Folate-targeted drug strategies for the treatment of cancer Curr. Opin. Invest. Drugs 9, 1277-86
4. Bailey SW, A. J. (2009) The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake Proc. Natl. Acad. Sci. U. S. A. 106, 15424-15429
5. Westerhof, G. R., Schornagel, J. H., Kathmann, I., Jackman, A. L., Rosowsky, A., Forsch, R. A., Hynes, J. B., Boyle, F. T., Peters, G. J., Pinedo, H. M., and Jansen, G. (1995) Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: Correlates of molecular structure and biological activity Mol. Pharmacol. 48, 459-471
6. Leamon, C. P., You, F., Santhapuram, H. K., Fan, M., and Vlahov, I. R. (2009) Properties influencing the relative binding affinity of pteroate derivatives and drug conjugates thereof to the folate receptor Pharm. Res. 26, 1315-23
7. Leamon, C. P. and Low, P. S. (1993) Membrane folate-binding proteins are responsible for folate- protein conjugate endocytosis into cultured cells Biochem. J. 291, 855-860
8. Lee, R. J., Wang, S., and Low, P. S. (1996) Measurement of endosome pH following folate receptor-mediated endocytosis Biochim. Biophys. Acta 1312, 237-42
9. Leamon, C. P. and Jackman, A. L. (2008) Exploitation of the Folate Receptor in the Management of Cancer and Inflammatory Disease, in Vitamins and Hormones (Litwack, G., Ed.) pp 203-233.
10. Leamon, C. P. and Reddy, J. A. (2004) Folate-targeted chemotherapy Adv. Drug Delivery Rev. 56, 1127-1141
11. Steinberg, G. and Borch, R. F. (2001) Synthesis and evaluation of pteroic acid-conjugated nitroheterocyclic phosphoramidates as folate receptor-targeted alkylating agents J. Med. Chem. 44, 69-73
12. Aronov, O., Horowitz, A. T., Gabizon, A., and Gibson, D. (2003) Folate-targeted PEG as a potential carrier for Carboplatin analogs. Synthesis and in vitro studies Bioconjugate Chem. 14, 563-74
13. Liu, J. Q., Kolar, C., Lawson, T. A., and Gmeiner, W. H. (2001) Targeted drug delivery to chemoresistant cells: Folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells J. Org. Chem. 66, 5655-5663
14. Lee, J. W., Lu, J. Y., Low, P. S., and Fuchs, P. L. (2002) Synthesis and evaluation of taxol-folic acid conjugates as targeted antineoplastics Bioorg. Med. Chem. 10, 2397-414
15. Leamon, C. P., Pastan, I., and Low, P. S. (1993) Cytotoxicity of folate-pseudomonas exotoxin conjugates toward tumor cells J. Biol. Chem. 268, 24847-24854
16. Ladino, C. A., Chari, R. V. J., Bourret, L. A., Kedersha, N. L., and Goldmacher, V. S. (1997) Folate-maytansinoids: Target-selective drugs of low molecular weight Int. J. Cancer 73, 859-864
17. Leamon, C. P., Reddy, J. A., Vlahov, I. R., Westrick, E., Parker, N., Nicoson, J. S., and Vetzel, M. (2007) Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145 Int. J. Cancer 121, 1585-92
18. Leamon, C. P. (2003) Folate-targeted chemotherapy: In vitro and in vivo activity of EC72. In Proceedings of the American Association for Cancer Research 44, Abstract # 2627, page 600.
19. Leamon, C. P., Reddy, J. A., Vetzel, M., Dorton, R., Westrick, E., Parker, N., Wang, Y., and Vlahov, I. (2008) Folate targeting enables durable and specific antitumor responses from a therapeutically null tubulysin B analogue Cancer Res. 68, 9839-44
20. Reddy, J. A., Dorton, R., Dawson, A., Vetzel, M., Parker, N., Nicoson, J. S., Westrick, E., Klein, P. J., Wang, Y., Vlahov, I. R., and Leamon, C. P. (2009) In vivo structural activity and optimization studies of folate-tubulysin conjugates Mol. Pharm. 6, 1518-25
21. Parker, N., Turk, M. J., Westrick, E., Lewis, J. D., Low, P. S., and Leamon, C. P. (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay Anal. Biochem. 338, 284-93
22. Paulos, C. M., Reddy, J. A., Leamon, C. P., Turk, M. J., and Low, P. S. (2004) Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery Mol. Pharmacol. 66, 1406-14
23. Yang, J., Chen, H., Vlahov, I. R., Cheng, J. X., and Low, P. S. (2006) Evaluation of disulfide reduction during receptor-mediated endocytosis using fluorescence resonance energy transfer imaging Proc. Natl. Acad. Sci. U. S. A. 103, 13872-13877
24. Yang, J., Chen, H., Vlahov, I. R., Cheng, J. X., and Low, P. S. (2007) Characterization of the pH of folate receptor-containing endosomes and the rate of hydrolysis of internalized acid-labile folate-drug conjugates J. Pharmacol. Exp. Ther. 321, 462-8
25. Lee, R. J., Wang, S., Turk, M. J., and Low, P. S. (1998) The effects of pH and intraliposomal buffer strength on the rate of liposome content release and intracellular drug delivery Biosci. Rep. 18, 69-78
26. Vlahov, I. R., Santhapuram, H. K., Kleindl, P. J., Howard, S. J., Stanford, K. M., and Leamon, C. P. (2006) Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part 1: EC145, a folic acid conjugate of desacetylvinblastine monohydrazide Bioorg. Med. Chem. Lett. 16, 5093-6
27. Vlahov, I. R., Wang, Y., Kleindl, P. J., and Leamon, C. P. (2008) Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part II: Folic acid conjugates of tubulysins and their hydrazides Bioorg. Med. Chem. Lett. 18, 4558-61
28. Vlahov, I. R., Vite, G. D., Kleindl, P. J., Wang, Y., Santhapuram, H. K., You, F., Howard, S. J., Kim, S. H., Lee, F. F., and Leamon, C. P. (2010) Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid Bioorg. Med. Chem. Lett. 20, 4578-81
29. Reddy, J. A., Westrick, E., Santhapuram, H. K., Howard, S. J., Miller, M. L., Vetzel, M., Vlahov, I., Chari, R. V., Goldmacher, V. S., and Leamon, C. P. (2007) Folate Receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate Cancer Res. 67, 6376-82
30. Henne, W. A., Doorneweerd, D. D., Hilgenbrink, A. R., Kularatne, S. A., and Low, P. S. (2006) Synthesis and activity of a folate peptide camptothecin prodrug Bioorg. Med. Chem. Lett. 16, 5350-5
31. Satyam, A. (2008) Design and synthesis of releasable folate-drug conjugates using a novel heterobifunctional disulfide-containing linker Bioorg. Med. Chem. Lett. 18, 3196-3199
32. Suzuki, T., Hisakawa, S., Itoh, Y., Suzuki, N., Takahashi, K., Kawahata, M., Yamaguchi, K., Nakagawa, H., and Miyata, N. (2007) Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors Bioorg. Med. Chem. Lett. 17, 4208-12
33. Reddy, J. A., Dorton, R., Westrick, E., Dawson, A., Smith, T., Xu, L. C., Vetzel, M., Kleindl, P., Vlahov, I. R., and Leamon, C. P. (2007) Preclinical evaluation of EC145, a folate-vinca alkaloid conjugate Cancer Res. 67, 4434-42
34. Covello, K. L., Flefleh, C., Menard, K., Wiebesiek, A., Mcglinchey, K., Wen, M. L., Westhouse, R., Reddy, J. A., Vlahov, I. R., Hunt, J., Rose, W., Leamon, C. P., Vite, G., and Lee, F. (2008) in Proceedings of the 99th Annual Meeting of AACR, San Diego, CA.
35. Sausville, E., LoRusso, P., Quinn, M., Forman, K., Leamon, C., Morganstern, D., Bever, S., and Messmann, R. (2007) A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors Proc. Am. Soc. Clin. Oncol. 25, 2577
36. Naumann, R. W. and Coleman, R. L. (2011) Management strategies for recurrent platinum-resistant ovarian cancer Drugs 71, 1397-412
37. Naumann, R. W., Morris, R., Harb, W., Micha, J., Sutton, G., Dinh, T., Mcintyre, J., Patel, R., Davidson, J., Hu, E., and Messmann, R. (2009) in 16th International Meeting European Society Gynecological Oncology, Abstract 1181.
38. Symanowski, J. T., Maurer, A. H., Naumann, R. W., Shah, N. P., Morgenstern, D., and Messmann, R. A. J. Clin. Oncol. 2010, 28 (15) Suppl. Abstr. 5034.
39. Vlahov, I. R., Leamon, C. P., Parker, M., Howard, S., Santhapuram, H., Satyam, A., and Reddy, J. (2009) Vitamin receptor binding drug delivery conjugates. U.S. Patent 7,601,332 B2.
40. Leamon, C. P. and Low, P. S. (2005) Receptor-Mediated Drug Delivery, in Drug Delivery: Principles and Applications (Wang, B., Siahaan, T., and Soltero, R. A., Eds.) pp 167-183, Hoboken.
41. Ducry, L. and Stump, B. (2009) Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies Bioconjugate Chem. 21, 5-13
42. Li, J., Sausville, E. A., Klein, P. J., Morgenstern, D., Leamon, C. P., Messmann, R. A., and LoRusso, P. (2009) Clinical pharmacokinetics and exposure-toxicity relationship of a folate-Vinca alkaloid conjugate EC145 in cancer patients J. Clin. Pharmacol. 49, 1467-76
43. Oae, S. (1977) Organic Chemistry of Sulfur, Plenum, New York.
44. Oae, S. (1985) Historical development of sulphur bonding: A view of an experimental organosulphur chemist, Elsevier, New York.
45. Vlahov, I. R., Santhapuram, H. K., Wang, Y., Kleindl, P. J., You, F., Howard, S. J., Westrick, E., Reddy, J. A., and Leamon, C. P. (2007) An assembly concept for the consecutive introduction of unsymmetrical disulfide bonds: synthesis of a releasable multidrug conjugate of folic acid J. Org. Chem. 72, 5968-72
46. Leamon, C. P., Reddy, J. A., Vlahov, I. R., Westrick, E., Dawson, A., Dorton, R., Vetzel, M., Santhapuram, H. K., and Wang, Y. (2007) Preclinical antitumor activity of a novel folate-targeted dual drug conjugate Mol. Pharm. 4, 659-67
47. Vlahov, I. R., Santhapuram, H. K., You, F., Wang, Y., Kleindl, P. J., Hahn, S. J., Vaughn, J. F., Reno, D. S., and Leamon, C. P. (2010) Carbohydrate-based synthetic approach to control toxicity profiles of folate-drug conjugates J. Org. Chem. 75, 3685-91
48. Leamon, C. P., Reddy, J. A., Klein, P. J., Vlahov, I. R., Dorton, R., Bloomfield, A., Nelson, M., Westrick, E., Parker, N., Bruna, K., Vetzel, M., Gehrke, M., Nicoson, J. S., Messmann, R. A., LoRusso, P. M., and Sausville, E. A. (2011) Reducing undesirable hepatic clearance of a tumor-targeted vinca alkaloid via novel saccharopeptidic modifications J. Pharmacol. Exp. Ther. 336, 336-43
49. Kamen, B. A., Smith, A. K., and Anderson, R. G. W. (1991) The folate receptor works in tandem with a probenecid-sensitive carrier in MA104 cells in vitro J. Clin. Invest. 87, 1442-1449
50. Leamon, C. P., Reddy, J. A., Vlahov, I. R., Kleindl, P. J., Vetzel, M., and Westrick, E. (2006) Synthesis and biological evaluation of EC140: A novel folate-targeted vinca alkaloid conjugate Bioconjugate Chem. 17, 1226-32
51. Low, P. S., Henne, W. A., and Doorneweerd, D. D. (2008) Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases Acc. Chem. Res. 41, 120-9
52. Leamon, C. P. and Low, P. S. (1991) Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis Proc. Natl. Acad. Sci. U.S.A. 88, 5572-5576
53. Turek, J. J., Leamon, C. P., and Low, P. S. (1993) Endocytosis of folate-protein conjugates: ultrastructural localization in KB cells J. Cell Sci. 106 (Pt 1) 423-30
54. Kularatne, S. A., Venkatesh, C., Santhapuram, H. K., Wang, K., Vaitilingam, B., Henne, W. A., and Low, P. S. (2010) Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs J. Med. Chem. 53, 7767-77