A new triglycyl peptide linker for antibody-drug conjugates (ADCs) with improved targeted killing of cancer cells

Molecular Cancer Therapeutics

Volumn 15, Issue 6, 2016, Pages 1311-1320

  Singh, Rajeeva ^a   Setiady, Yulius Y ^a   Ponte, Jose ^a   Kovtun, Yelena V ^a   Lai, Katharine C ^a   Hong, E Erica ^a   Fishkin, Nathan ^a   Dong, Ling ^a   Jones, Gregory E ^a   Coccia, Jennifer A ^a,b   Lanieri, Leanne ^a   Veale, Karen ^a   Costoplus, Juliet A ^a   Skaletskaya, Anna ^a   Gabriel, Rabih ^a   Salomon, Paulin ^a   Wu, Rui ^a   Qiu, Qifeng ^a   Erickson, Hans K ^a,c   Lambert, John M ^a   Chari, Ravi V J ^a   Widdison, Wayne C ^a   more..

^a ImmunoGen   (United States)

^b REGENERON PHARMACEUTICALS INC   (United States)

^c GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY CONJUGATE; CARBOXYLIC ACID; EPITHELIAL CELL ADHESION MOLECULE; SMCC ANTIBODY CONJUGATE; TRIGLYCYL PEPTIDE LINKER ANTIBODY CONJUGATE; UNCLASSIFIED DRUG; EGFR PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR RECEPTOR; MAYTANSINE; PEPTIDE;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CANCER CELL LINE; CANCER TISSUE; CELL KILLING; CELL SURFACE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG METABOLISM; DRUG TOLERABILITY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LYSOSOME; MAXIMUM TOLERATED DOSE; MOUSE; MULTIPLE CANCER; NONHUMAN; PH; PRIORITY JOURNAL; TARGET CELL; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; NEOPLASMS; SCID MOUSE; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; EPITHELIAL CELL ADHESION MOLECULE; HUMANS; IMMUNOCONJUGATES; MAXIMUM TOLERATED DOSE; MAYTANSINE; MICE; MICE, SCID; NEOPLASMS; PEPTIDES; RECEPTOR, EPIDERMAL GROWTH FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84971509003     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-16-0021     Document Type: Article

References (36)

1. Chari RV, Miller ML, Widdison WC. Antibody-drug conjugates: an emerging concept in cancer therapy. Angew Chem Int Ed Engl 2014; 53:3796-827.
2. Singh R, Lambert JM, Chari RVJ. Antibody-drug conjugates (ADCs): new frontier in cancer therapeutics. In: Stefan Dubel, Janice M Reichert, editors Handbook of therapeutic antibodies, 2nd Edition Wiley-VCH2014. p. 341-62.
3. Katz J, Janik JE, Younes A. Brentuximab Vedotin (SGN-35). Clin Cancer Res 2011;17:6428-36.
4. Lambert JM, Chari RV. Ado-trastuzumab Emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer. J Med Chem 2014;57:6949-64.
5. Diamantis N, Banerji U. Antibody-drug conjugates-an emerging class of cancer treatment. Br J Cancer 2016;114:362-7.
6. Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 2011;17:3157-69.
7. DiJoseph JF, Armellino DC, Boghaert ER, Khandke K, Dougher MM, Sridharan L, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood 2004;103:1807-14.
8. Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, et al. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 2013;122:1455-63.
9. Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, et al. Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res 2005; 11:5257-64.
10. Elgersma RC, Coumans RG, Huijbregts T, Menge WM, Joosten JA, Spijker HJ, et al. Design, synthesis, and evaluation of linker-duocarmycin payloads: toward selection of HER2-targeting antibody-drug conjugate SYD985. Mol Pharm 2015;12:1813-35.
11. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 2006;66:4426-33.
12. Doronina SO, Mendelsohn BA, Bovee TD, Cerveny CG, Alley SC, Meyer DL, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem 2006;17:114-24.
13. Oroudjev E, Lopus M, Wilson L, Audette C, Provenzano C, Erickson H, et al. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol Cancer Ther 2010;9:2700-13.
14. Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, et al. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem 2010;21:84-92.
15. Kovtun YV, Audette CA, Ye Y, Xie H, Ruberti MF, Phinney SJ, et al. Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 2006;66:3214-21.
16. Widdison WC, Wilhelm SD, Cavanagh EE, Whiteman KR, Leece BA, Kovtun Y, et al. Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem 2006;49:4392-408.
17. Zhao RY, Wilhelm SD, Audette C, Jones G, Leece BA, Lazar AC, et al. Synthesis and evaluation of hydrophilic linkers for antibody-maytansinoid conjugates. J Med Chem 2011;54:3606-23.
18. Okeley NM, Miyamoto JB, Zhang X, Sanderson RJ, Benjamin DR, Sievers EL, et al. Intracellular activation of SGN-35, a potent anti-CD30 antibodydrug conjugate. Clin Cancer Res 2010;16:888-97.
19. Hamann PR, Hinman LM, Hollander I, Beyer CF, Lindh D, Holcomb R, et al. Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug Chem 2002;13:47-58.
20. Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol 2010; 28:2085-93.
21. Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEA-CAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res 2009;15:6052-61.
22. Kellogg BA, Garrett L, Kovtun Y, Lai KC, Leece B, Miller M, et al. Disulfidelinked antibody-maytansinoid conjugates: optimization of in vivo activity by varying the steric hindrance at carbon atoms adjacent to the disulfide linkage. Bioconjug Chem 2011;22:717-27.
23. Kovtun YV, Audette CA, Mayo MF, Jones GE, Doherty H, Maloney EK, et al. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res 2010;70:2528-37.
24. Elkins K, Zheng B, Go M, Slaga D, Du C, Scales SJ, et al. FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. Mol Cancer Ther 2012;11:2222-32.
25. de Bono JS, Tolcher AW, Forero A, Vanhove GF, Takimoto C, Bauer RJ, et al. ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clin Cancer Res 2004;10: 7555-65.
26. Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res 1987;47:2883-91.
27. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med 2008;358:1160-74.
28. Erickson HK, Lewis Phillips GD, Leipold DD, Provenzano CA, Mai E, Johnson HA, et al. The effect of different linkers on target cell catabolism and pharmacokinetics/pharmacodynamics of trastuzumab maytansinoid conjugates. Mol Cancer Ther 2012;11:1133-42.
29. Salomon PL, Singh R. Sensitive ELISA method for the measurement of catabolites of antibody-drug conjugates (ADCs) in target cancer cells. Mol Pharm 2015;12:1752-61.
30. Sun X, Widdison W, Mayo M, Wilhelm S, Leece B, Chari R, et al. Design of antibody-maytansinoid conjugates allows for efficient detoxification via liver metabolism. Bioconjug Chem 2011;22:728-35.
31. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 2008;68: 9280-90.
32. Haggie PM, Verkman AS. Unimpaired lysosomal acidification in respiratory epithelial cells in cystic fibrosis. J Biol Chem 2009;284:7681-6.
33. Karuri AR, Dobrowsky E, Tannock IF. Selective cellular acidification and toxicity of weak organic acids in an acidic microenvironment. Br J Cancer 1993;68:1080-7.
34. Ellenbogen E. Dissociation constants of peptides. I. A survey of the effect of optical configuration. J Am Chem Soc 1952;74:5198-201.
35. Hamblett KJ, Jacob AP, Gurgel JL, Tometsko ME, Rock BM, Patel SK, et al. SLC46A3 is required to transport catabolites of noncleavable antibody maytansine conjugates from the lysosome to the cytoplasm. Cancer Res 2015;75:5329-40.
36. Widdison WC, Ponte JF, Coccia JA, Lanieri L, Setiady Y, Dong L, et al. Development of anilino-maytansinoid ADCs that efficiently release cytotoxic metabolites in cancer cells and induce high levels of bystander killing. Bioconjug Chem 2015;26:2261-78.