Development of Anilino-Maytansinoid ADCs that Efficiently Release Cytotoxic Metabolites in Cancer Cells and Induce High Levels of Bystander Killing

Bioconjugate Chemistry

Volumn 26, Issue 11, 2015, Pages 2261-2278

  Widdison, Wayne C ^a   Ponte, Jose F ^a   Coccia, Jennifer A ^a   Lanieri, Leanne ^a   Setiady, Yulius ^a   Dong, Ling ^a   Skaletskaya, Anna ^a   Hong, E Erica ^a   Wu, Rui ^a   Qiu, Qifeng ^a   Singh, Rajeeva ^a   Salomon, Paulin ^a   Fishkin, Nathan ^a   Harris, Luke ^a   Maloney, Erin K ^a   Kovtun, Yelena ^a   Veale, Karen ^a   Wilhelm, Sharon D ^a   Audette, Charlene A ^a   Costoplus, Juliet A ^a   Chari, Ravi V J ^a   more..

^a IMMUNOGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANILINE; MONOCLONAL ANTIBODIES; STEREOCHEMISTRY; SULFUR COMPOUNDS;

CANCER CELLS; CYTOTOXIC METABOLITE; DI-PEPTIDES; IN-VITRO; MICE MODELS; PEPTIDE LINKERS; PROPERTY;

PEPTIDES;

ANILINE DERIVATIVE; ANTIBODY ANILINO MAYTANSINOID CONJUGATE; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; DIPEPTIDE; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; MAYTANSINE; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CELL; CANCER CELL DESTRUCTION; CARBON NUCLEAR MAGNETIC RESONANCE; CELL METABOLISM; DRUG EFFICACY; DRUG STRUCTURE; DRUG SYNTHESIS; G2 PHASE CELL CYCLE CHECKPOINT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HT 29 CELL LINE; IN VITRO STUDY; METHYLATION; MOUSE; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; STEREOISOMERISM; TUMOR XENOGRAFT; ANIMAL; CELL CYCLE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; HUMAN; NEOPLASMS; TUMOR CELL LINE;

ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; CELL CYCLE; CELL LINE, TUMOR; CELL SURVIVAL; HUMANS; IMMUNOCONJUGATES; MAYTANSINE; MICE; NEOPLASMS;

EID: 84947912607     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/acs.bioconjchem.5b00430     Document Type: Article

References (35)

1. Erickson, H. K., Park, P. U., Widdison, W. C., Kovtun, Y. V., Garrett, L. M., Hoffman, K., Lutz, R. J., Goldmacher, V. S., and Blattler, W. A. (2006) Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing Cancer Res. 66, 4426-33
2. Sutherland, M. S., Sanderson, R. J., Gordon, K. A., Andreyka, J., Cerveny, C. G., Yu, C., Lewis, T. S., Meyer, D. L., Zabinski, R. F., and Doronina, S. O. et al. 2006, Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates J. Biol. Chem. 281, 10540-7 10.1074/jbc.M510026200
3. Sun, X., Widdison, W., Mayo, M., Wilhelm, S., Leece, B., Chari, R., Singh, R., and Erickson, H. (2011) Design of antibody-maytansinoid conjugates allows for efficient detoxification via liver metabolism Bioconjugate Chem. 22, 728-35 10.1021/bc100498q
4. Sedlacek, H. H. (1992) Antibodies as carriers of cytotoxicity; Karger: Basel, New York.
5. Heine, M., Freund, B., Nielsen, P., Jung, C., Reimer, R., Hohenberg, H., Zangemeister-Wittke, U., Wester, H. J., Luers, G. H., and Schumacher, U. (2012) High interstitial fluid pressure is associated with low tumour penetration of diagnostic monoclonal antibodies applied for molecular imaging purposes PLoS One 7, e36258 10.1371/journal.pone.0036258
6. Vasalou, C., Helmlinger, G., and Gomes, B. (2015) A mechanistic tumor penetration model to guide antibody drug conjugate design PLoS One 10, e0118977 10.1371/journal.pone.0118977
7. Fujimori, K., Covell, D. G., Fletcher, J. E., and Weinstein, J. N. (1989) Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab′)2, and Fab in tumors Cancer Res. 49, 5656-63
8. Juweid, M., Neumann, R., Paik, C., Perez-Bacete, M. J., Sato, J., van Osdol, W., and Weinstein, J. N. (1992) Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier Cancer Res. 52, 5144-53
9. Mitsiades, C. S., Mitsiades, N. S., Munshi, N. C., Richardson, P. G., and Anderson, K. C. (2006) The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions Eur. J. Cancer 42, 1564-73 10.1016/j.ejca.2005.12.025
10. Bremnes, R. M., Donnem, T., Al-Saad, S., Al-Shibli, K., Andersen, S., Sirera, R., Camps, C., Marinez, I., and Busund, L. T. (2011) The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer J. Thorac. Oncol. 6, 209-17 10.1097/JTO.0b013e3181f8a1bd
11. Kovtun, Y. V., Audette, C. A., Ye, Y., Xie, H., Ruberti, M. F., Phinney, S. J., Leece, B. A., Chittenden, T., Blaettler, 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 10.1158/0008-5472.CAN-05-3973
12. Kellogg, B. A., Garrett, L., Kovtun, Y., Lai, K. C., Leece, B., Miller, M., Payne, G., Steeves, R., Whiteman, K. R., and Widdison, W. et al. 2011, Disulfide-linked antibody-maytansinoid conjugates: optimization of in vivo activity by varying the steric hindrance at carbon atoms adjacent to the disulfide linkage Bioconjugate Chem. 22, 717-27 10.1021/bc100480a
13. Ab, O., Whiteman, K. R., Bartle, L. M., Sun, X., Singh, R., Tavares, D., LaBelle, A., Payne, G., Lutz, R. J., and Pinkas, J. et al. 2015, IMGN853, a Folate Receptor-alpha (FRalpha)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRalpha-Expressing Tumors Mol. Cancer Ther. 14, 1605-13 10.1158/1535-7163.MCT-14-1095
14. Okeley, N. M., Miyamoto, J. B., Zhang, X., Sanderson, R. J., Benjamin, D. R., Sievers, E. L., Senter, P. D., and Alley, S. C. (2010) Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate Clin. Cancer Res. 16, 888-97 10.1158/1078-0432.CCR-09-2069
15. Borghaei, H., O'Malley, D. D., Seward, S. M., Bauer, T. M., Perez, R. P., and Oza, A. M. (2015) Phase 1 study of IMGN853, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) in patients (Pts) with epithelial ovarian cancer (EOC) and other FRA-positive solid tumors. J. Clin. Oncol. 33, Abstract 5558.
16. Krop, I. E., Beeram, M., Modi, S., Jones, S. F., Holden, S. N., Yu, W., Girish, S., Tibbitts, J., Yi, J. H., and Sliwkowski, M. X. et al. 2010, Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer J. Clin. Oncol. 28, 2698-704 10.1200/JCO.2009.26.2071
17. Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., Pegram, M., Oh, D. Y., Dieras, V., and Guardino, E. et al. 2012, Trastuzumab emtansine for HER2-positive advanced breast cancer N. Engl. J. Med. 367, 1783-91 10.1056/NEJMoa1209124
18. 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, 855-69 10.1021/bc025536j
19. Jeffrey, S. C., Burke, P. J., Lyon, R. P., Meyer, D. W., Sussman, D., Anderson, M., Hunter, J. H., Leiske, C. I., Miyamoto, J. B., and Nicholas, N. D. et al. 2013, A Potent Anti-CD70 Antibody-Drug Conjugate Combining a Dimeric Pyrrolobenzodiazepine Drug with Site-Specific Conjugation Technology Bioconjugate Chem. 24, 1256 10.1021/bc400217g
20. Bryson, A. (1960) The Effects of m-Substituents on the pKa Values of Anilines, and on the Stretching Frequencies of the N-H Bonds J. Am. Chem. Soc. 82, 4858-4862 10.1021/ja01503a028
21. Widdison Wayne, C., Wilhelm Sharon, D., Cavanagh Emily, E., Whiteman Kathleen, R., Leece Barbara, A., Kovtun, Y., Goldmacher Victor, S., Xie, H., Steeves Rita, M., and Lutz Robert, J. et al. 2006, Semisynthetic maytansine analogues for the targeted treatment of cancer J. Med. Chem. 49, 4392-408 10.1021/jm060319f
22. Drose, S. and Altendorf, K. (1997) Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases J. Exp. Biol. 200, 1-8
23. van Weert, A. W., Dunn, K. W., Geuze, H. J., Maxfield, F. R., and Stoorvogel, W. (1995) Transport from late endosomes to lysosomes, but not sorting of integral membrane proteins in endosomes, depends on the vacuolar proton pump J. Cell Biol. 130, 821-34 10.1083/jcb.130.4.821
24. Salomon, P. L. and Singh, R. (2015) Sensitive ELISA Method for the Measurement of Catabolites of Antibody-Drug Conjugates (ADCs) in Target Cancer Cells Mol. Pharmaceutics 12, 1752-61 10.1021/acs.molpharmaceut.5b00028
25. Bissery, M. C., Guenard, D., Gueritte-Voegelein, F., and Lavelle, F. (1991) Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue Cancer Res. 51, 4845-52
26. Xie, H., Audette, C., Hoffee, M., Lambert, J. M., and Blattler, 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, 1073-82 10.1124/jpet.103.060533
27. Hong, E. E., Erickson, H., Lutz, R. J., Whiteman, K. R., Jones, G., Kovtun, Y., Blanc, V., and Lambert, J. M. (2015) Design of Coltuximab Ravtansine, a CD19-Targeting Antibody-Drug Conjugate (ADC) for the Treatment of B-Cell Malignancies: Structure-Activity Relationships and Preclinical Evaluation Mol. Pharmaceutics 12, 1703-16 10.1021/acs.molpharmaceut.5b00175
28. Lin, D., Saleh, S., and Liebler, D. C. (2008) Reversibility of covalent electrophile-protein adducts and chemical toxicity Chem. Res. Toxicol. 21, 2361-9 10.1021/tx800248x
29. Baldwin, A. D. and Kiick, K. L. (2011) Tunable degradation of maleimide-thiol adducts in reducing environments Bioconjugate Chem. 22, 1946-53 10.1021/bc200148v
30. Golfier, S., Kopitz, C., Kahnert, A., Heisler, I., Schatz, C. A., Stelte-Ludwig, B., Mayer-Bartschmid, A., Unterschemmann, K., Bruder, S., and Linden, L. et al. 2014, Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect Mol. Cancer Ther. 13, 1537-48 10.1158/1535-7163.MCT-13-0926
31. Xia, T. S., Wang, J., Yin, H., Ding, Q., Zhang, Y. F., Yang, H. W., Liu, X. A., Dong, M., Du, Q., and Ling, L. J. et al. 2010, Human tissue-specific microenvironment: an essential requirement for mouse models of breast cancer Oncol. Rep. 24, 203-11
32. Roussel, M. F., Downing, J. R., Rettenmier, C. W., and Sherr, C. J. (1988) A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential Cell 55, 979-88 10.1016/0092-8674(88)90243-7
33. Bhargava, M., Joseph, A., Knesel, J., Halaban, R., Li, Y., Pang, S., Goldberg, I., Setter, E., Donovan, M. A., and Zarnegar, R. et al. 1992, Scatter factor and hepatocyte growth factor: activities, properties, and mechanism Cell Growth Differentiation 3, 11-20
34. Yu, D. D., Wu, Y., Shen, H. Y., Lv, M. M., Chen, W. X., Zhang, X. H., Zhong, S. L., Tang, J. H., and Zhao, J. H. (2015) Exosomes in Development, Metastasis and Drug Resistance of Breast Cancer Cancer science 106, 959 10.1111/cas.12715
35. Fusek, M., Vetvickova, J., and Vetvicka, V. (2007) Secretion of cytokines in breast cancer cells: the molecular mechanism of procathepsin D proliferative effects J. Interferon Cytokine Res. 27, 191-9 10.1089/jir.2006.0105