Antibody-drug conjugates: Linking cytotoxic payloads to monoclonal antibodies

Bioconjugate Chemistry

Volumn 21, Issue 1, 2010, Pages 5-13

  Ducry, Laurent ^a   Stump, Bernhard ^a  

^a LONZA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

SURFACE PLASMON RESONANCE;

ANTIBODY-DRUG CONJUGATES; BUILDING BLOCKES; CYTOTOXIC; CYTOTOXINS; TUMOUR CELLS;

MONOCLONAL ANTIBODIES;

ALKYLATING AGENT; CYCLOPROPAPYRROLOIND 4 ONE DERIVATIVE; CYTOTOXIC AGENT; DOXORUBICIN; DUOCARMYCIN DERIVATIVE; GEMTUZUMAB OZOGAMICIN; INOTUZUMAB OZOGAMICIN; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY BR96; MONOMETHYLAURISTATIN E; MONOMETHYLAURISTATIN F; RACHELMYCIN; UNCLASSIFIED DRUG; VASCULAR TARGETING AGENT;

ACUTE GRANULOCYTIC LEUKEMIA; ANTIBODY SPECIFICITY; ANTIGEN ANTIBODY COMPLEX; ANTIGEN BINDING; CARCINOMA CELL; COMPLEX FORMATION; COVALENT BOND; CYTOTOXICITY; DISULFIDE BOND; DNA REPLICATION; DRUG HALF LIFE; DRUG POTENCY; HUMAN; IC 50; MOLECULAR WEIGHT; NONHUMAN; REVIEW; TUMOR CELL;

EID: 74949107560     PISSN: 10431802     EISSN: None     Source Type: Journal    
DOI: 10.1021/bc9002019     Document Type: Review

References (50)

1. Kratz, F., Müller, I. A., Ryppa, C., and Warnecke, A. (2008) Prodrug strategies in anticancer chemotherapy. ChemMedChem 3, 20-53.
2. Panchal, R. G. (1998) Novel therapeutic strategies to selectively kill cancer cells. Biochem. Pharmacol. 55, 247-252.
3. Zangemeister-Wittke, U. (2005) Antibodies for targeted cancer therapy - technical aspects and clinical perspectives. Pathobiology 72, 279-286.
4. Monoclonal antibodies conjugated with radioisotopes do not have to release their payload at the target site and need thus completely different linkers that mAb conjugated with cytotoxins. They are not reviewed in this article. For a review, see Wu, A. M., and Senter, P. D. (2005) Arming antibodies: Prospects and challenges for immunoconjugates. Nat. Biotechnol. 23, 1137-1146.
5. Ricart, A. D., and Tolcher, A. W. (2007) Technology insight: Cytotoxic drug immunoconjugates for cancer therapy. Nat. Clin. Pract. Oncol. 4, 245-255.
6. Carter, P. J., and Senter, P. D. (2008) Antibody-drug conjugates for cancer therapy. Cancer J. 14, 154-169.
7. Rohrer, T. (2008) New weapons for the oncology arsenal. Chem. Rundschau 9, 26-28.
8. Hamblett, K. J., Senter, P. D., Chace, D. F., Sun, M. M. C., Lenox, J., Cerveny, C. G., Kissler, K. M., Bernhardt, S. X., Kopcha, A. K., Zabinski, R. F., Meyer, D. L., and Francisco, J. A. (2004) Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin. Cancer Res. 10, 7063-7070.
9. McDonagh, C. F., Turcott, E., Westendorf, L., Webster, J. B., Alley, S. C., Kim, K., Andreyka, J., Stone, I., Hamblett, K. J., Francisco, J. A., and Carter, P. (2006) Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Prot. Eng. Des. Sel. 19, 299-307.
10. Trail, P. A., Willner, D., Lasch, S. J., Henderson, A. J., Hofstead, S., Casazza, A. M., Firestone, R. A., Hellström, I., and Hellström, K. E. (1993) Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261, 212-215.
11. Dubowchik, G. M., Firestone, R. A., Padilla, L., Willner, D., Hofstead, S. J., Mosure, K., Knipe, J. O., Lasch, S. J., and Trail, P. A. (2002) Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: Model studies of enzymatic drug release and antigen specific in vitro anticancer activity. Bioconjugate Chem. 13, 855-869.
12. Hamann, P. R., Hinman, L. M., Beyer, C. F., Lindh, D., Upeslacis, J., Flowers, D. A., and Bernstein, I. (2002) An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukaemia. Choice of linker. Bioconjugate Chem. 13, 40-46.
13. Hamann, P. R., Hinman, L. M., Hollander, I., Beyer, C. F., Lindh, D., Holcomb, R., Hallett, W., Tsou, H.-R., Upeslacis, J., Shochat, D., Mountain, A., Flowers, D. A., and Bernstein, I. (2002) Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjugate Chem. 13, 47-58.
14. Hollander, I., Kunz, A., and Hamann, P. R. (2008) Selection of reaction additives used in the preparation of monomeric antibody-calicheamicin conjugates. Bioconjugate Chem. 19, 358-361.
15. van der Velden, V. H. J., te Marvelde, J. G., Hoogeveen, P. G., Bernstein, I. D., Houtsmuller, A. B., Berger, M. S., and van Dongen, J. J. M. (2001) Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood 97, 3197-3204.
16. Hamann, P. R., Hinman, L. M., Beyer, C. F., Lindh, D., Upeslacis, J., Shochat, D., and Mountain, A. (2005) A calicheamicin conjugate with a fully humanized anti-MUC1 antibody shows potent antitumor effects in breast and ovarian tumor xenografts. Bioconjugate Chem. 16, 354-360.
17. DiJoseph, J. F., Dougher, M. M., Kalyandrug, L. B., Armellino, D. C., Boghaert, E. R., Hamann, P. R., Moran, J. K., and Damle, N. K. (2006) Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin's B-cell lymphoma. Clin. Cancer Res. 12, 242-249.
18. DiJoseph, J. F., Khandke, K., Dougher, M. M., Evans, D. Y., Armellino, D. C., Hamann, P. R., and Damle, N. K. (2008) CMC-544 (inotuzumab ozogamicin): A CD22-targeted immunoconjugate of calicheamicin. Hematology Meeting Reports 5, 74-77.
19. Ojima, I., Geng, X., Wu, X., Qu, C., Borella, C. P., Xie, H., Wilhelm, S. D., Leece, B. A., Bartle, L. M., Goldmacher, V. S., and Chari, R. V. J. (2002) Tumor-specific novel taxoidmonoclonal antibody conjugates. J. Med. Chem. 45, 5620-5623.
20. Ranson, M., and Sliwkowski, M. X. (2002) Perspectives on anti-HER monoclonal antibodies. Oncology 63 (suppl. 1), 17-24.
21. Widdison, W. C., Wilhelm, S. D., Cavanagh, E. E., Whiteman, K. R., Leece, B. A., Kovtun, Y., Goldmacher, V. S., Xie, H., Steeves, R. M., Lutz, R. J., Zhao, R., Wang, L., Blättler, W. A., and Chari, R. V. J. (2006) Semisynthetic maytansine analogues for the targeted treatment of cancer. J. Med. Chem. 49, 4392-4408.
22. Erickson, H. K., Park, P. U., Widdison, W. C., Kovtun, Y. V., Garrett, L. M., Hoffman, K., Lutz, R. J., Goldmacher, V. S., and Blättler, W. A. (2006) Antibody-Maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 66, 4426-4433.
23. Kovtun, Y. V., Audette, C. A., Ye, Y., Xie, H., Ruberti, M. F., Phinney, S. J., Leece, B. A., Chittenden, T., Blättler, W. A., and Goldmacher, V. S. (2006) Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res. 66, 3214-3221.
24. Xie, H., Audette, C., Hoffee, M., Lambert, J. M., and Blättler, W. A. (2004) Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. J. Pharmacol. Exp. Ther. 308, 1073-1082.
25. Koblinski, J. E., Ahram, M., and Sloane, B. F. (2000) Unraveling the role of proteases in cancer. Clin. Chim. Acta 291, 113-135.
26. Doronina, S. O., Toki, B. E., Torgov, M. Y., Mendelsohn, B. A., Cerveny, C. G., Chace, D. F., DeBlanc, R. L., Gearing, R. P., Bovee, T. D., Siegall, C. B., Francisco, J. A., Wahl, A. F., Meyer, D. L., and Senter, P. D. (2003) Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 21, 778-784.
27. Toki, B. E., Cerveny, C. G., Wahl, A. F., and Senter, P. D. (2002) Protease-mediated fragmentation of p-amidobenzyl ethers: A new strategy for the activation of anticancer prodrugs. J. Org. Chem. 67, 1866-1872.
28. Sanderson, R. J., Hering, M. A., James, S. F., Sun, M. M. C., Doronina, S. O., Siadak, A. W., Senter, P. D., and Wahl, A. F. (2005) In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin. Cancer Res. 11, 843-852.
29. Francisco, J. A., Cerveny, C. G., Meyer, D. L., Mixan, B. J., Klussman, K., Chace, D. F., Rejniak, S. X., Gordon, K. A., DeBlanc, R., Toki, B. E., Law, C.-L., Doronina, S. O., Siegall, C. B., Senter, P. D., and Wahl, A. F. (2003) cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 102, 1458-1465.
30. Bartlett, N., Forero-Torres, A., Rosenblatt, J., Fanale, M., Horning, S. J., Thompson, S., Sievers, E. L., and Kennedy, D. A. (2009) Complete remissions with weekly dosing of SGN-35, a novel antibody-dug conjugate (ADC) targeting CD30, in phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). J. Clin. Oncol. 27, 8500.
31. Doronina, S. O., Bovee, T. D., Meyer, D. W., Miyamoto, J. B., Anderson, M. E., Morris-Tilden, C. A., and Senter, P. D. (2008) Novel peptide linkers for highly potent antibody-auristatin conjugate. Bioconjugate Chem. 19, 1960-1963.
32. Jeffrey, S. C., Nguyen, M. T., Andreyka, J. B., Meyer, D. L., Doronina, S. O., and Senter, P. D. (2006) Dipeptide-based highly potent doxorubicin antibody conjugates. Bioorg. Med. Chem. Lett. 16, 358-362.
33. Boger, D. L., Boyce, C. W., Garbaccio, R. M., Searcey, M., and Jin, Q. (1999) CBI prodrug analogs of CC-1065 and the duocarmycins. Synthesis 1505-1509, and references cited therein.
34. Nagamura, S., Kanda, Y., Kobayashi, E., Gomi, K., and Saito, H. (1995) Synthesis and antitumor activity of duocarmycin derivatives. Chem. Pharm. Bull. 43, 1530-1535.
35. 1θ-3 participation. Isolation and behavior of spiro(2,5)octa-1,4-diene-3-one. J. Am. Chem. Soc. 85, 567-578.
36. Wang, Y., Li, L., Tian, Z., Jiang, W., and Larrick, J. W. (2006) Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 14, 7854-7861.
37. Chen, L., Gangwar, S., Guerlavais, V., Lonberg, N., Zhang, Q. Chemical linkers with single amino acids and conjugates thereof, international patent application, WO 2008/103693 A2.
38. Longberg, N. (2008) Medarex '2008 R&D Day', New York City.
39. Tietze, L. F., Feuerstein, T., Fecher, A., Haunert, F., Panknin, O., Borchers, U., Schuberth, I., and Alves, F. (2002) Proof of principle in the selective treatment of cancer by antibody-directed enzyme prodrug therapy: The development of a highly potent prodrug. Angew. Chem., Int. Ed. 41, 759-761.
40. Tietze, L. F., Herzig, T., Feuerstein, T., and Schuberth, I. (2002) Synthesis and biological evaluation of novel analogues and prodrugs of the cytotoxic antibiotic CC-1065 for selective cancer therapy. Eur. J. Org. Chem. 1634-1645.
41. Tietze, L. F., Major, F., Schuberth, I., Spiegl, D. A., Krewer, B., Maksimenka, K., Bringmann, G., and Magull, J. (2007) Selective treatment of cancer: Synthesis, biological evaluation and structural elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins. Chem. - Eur. J. 13, 4396-4409.
42. Beusker, P. H., de Groot, F. M. H., Tietze, L. F., Major, F., Joosten, J. A. F., Spijker, H. J. Water-soluble CC-1065 analogs and their conjugates, international patent application, WO 2007/089149 A2.
43. Jeffrey, S. C., Torgov, M. Y., Andreyka, J. B., Boddington, L., Cerveny, C. G., Denny, W. A., Gordon, K. A., Gustin, D., Haugen, J., Kline, T., Nguyen, M. T., and Senter, P. D. (2005) Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates. J. Med. Chem. 48, 1344-1358.
44. Jeffrey, S. C., Nguyen, M. T., Moser, R. F., Meyer, D. L., Miyamoto, J. B., and Senter, P. D. (2007) Minor groove binder antibody conjugates employing a water soluble β-glucuronide linker. Bioorg. Med. Chem. Lett. 17, 2278-2280.
45. Burke, P. J., Senter, P. D., Meyer, D. W., Miyamoto, J. B., Anderson, M., Toki, B. E., Manikumar, G., Wani, M. C., Kroll, D. J., and Jeffrey, S. C. (2009) Design, synthesis, and biological evaluation of antibody-drug conjugates comprised of potent Camptothecin analogues. Bioconjugate Chem. 20, 1242-1250.
46. Chari, R. V. J. (2008) Targeted cancer therapy: Conferring specificity to cytotoxic drugs. Acc. Chem. Res. 41, 98-107.
47. Polson, A. G., Calemine-Fenaux, J., Chan, P., Chang, W., Christensen, E., Clark, S., de Sauvage, F. J., Eaton, D., Elkins, K., Elliott, J. M., Frantz, G., Fuji, R. N., Gray, A., Harden, K., Ingle, G. S., Kljavin, N. M., Koeppen, H., Nelson, C., Prabhu, S., Raab, H., Ross, S., Stephan, J.-P., Scales, S. J., Spencer, S. D., Vandlen, R., Wranik, B., Yu, S.-F., Zheng, B., and Ebens, A. (2009) Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: Target and linker-drug selection. Cancer Res. 69, 2358-2364.
48. Vogel, C. L., Burris, H. A., Limentani, S., Borson, R., O'Shaughnessy, J., Vukelja, S., Agresta, S., Klencke, B., Birkner, M., and Rugo, H. (2009) A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results. J. Clin. Oncol. 27:15s (suppl; abstr 1017).
49. Doronina, S. O., Mendelsohn, B. A., Bovee, T. D., Cerveny, C. G., Alley, S. C., Meyer, D. L., Oflazoglu, E., Toki, B. E., Sanderson, R. J., Zabinski, R. F., Wahl, A. F., and Senter, P. D. (2006) Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjugate Chem. 17, 114-124.
50. Alley, S. C., Benjamin, D. R., Jeffrey, S. C., Okeley, N. M., Meyer, D. L., Sanderson, R. J., and Senter, P. D. (2008) Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjugate Chem. 19, 759-765.