Site-specific trastuzumab maytansinoid antibody-drug conjugates with improved therapeutic activity through linker and antibody engineering

Journal of Medicinal Chemistry

Volumn 57, Issue 19, 2014, Pages 7890-7899

  Pillow, Thomas H ^a   Tien, Janet ^a   Parsons Reponte, Kathryn L ^a   Bhakta, Sunil ^a   Li, Hao ^a   Staben, Leanna R ^a   Li, Guangmin ^a   Chuh, Josefa ^a   Fourie Odonohue, Aimee ^a   Darwish, Martine ^a   Yip, Victor ^a   Liu, Luna ^a   Leipold, Douglas D ^a   Su, Dian ^a   Wu, Elmer ^a   Spencer, Susan D ^a   Shen, Ben Quan ^a   Xu, Keyang ^a   Kozak, Katherine R ^a   Raab, Helga ^a   Vandlen, Richard ^a   Lewis Phillips, Gail D ^a   Scheller, Richard H ^a   Polakis, Paul ^a   Sliwkowski, Mark X ^a   Flygare, John A ^a   Junutula, Jagath R ^a,b   more..

^a GENENTECH INC   (United States)

^b Cellerant Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRENTUXIMAB VEDOTIN; CYSTEINE; MALEIMIDE; MAYTANSINE; TRASTUZUMAB; TRASTUZUMAB EMTANSINE; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ANIMAL CELL; ANTIBODY DRUG CONJUGATE; ANTIBODY ENGINEERING; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CELL PROLIFERATION; CONTROLLED STUDY; DRUG CONJUGATION; DRUG SAFETY; DRUG SYNTHESIS; EPIMERIZATION; HODGKIN DISEASE; IN VITRO STUDY; MOUSE; NONHUMAN; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; HUMAN; PROTEIN ENGINEERING; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; HUMANS; IMMUNOCONJUGATES; MAYTANSINE; MICE; PROTEIN ENGINEERING;

EID: 84907929450     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500552c     Document Type: Article

References (32)

1. Mann, J. Natural Products in Cancer Chemotherapy: Past, Present and Future Nat. Rev. Cancer 2002, 2, 143-148
2. Cragg, G. M.; Grothaus, P. G.; Newman, D. J. Impact of Natural Products on Developing New Anti-Cancer Agents Chem. Rev. 2009, 109, 3012-3043
3. Scott, A. M.; Wolchok, J. D.; Old, L. J. Antibody Therapy of Cancer Nat. Rev. Cancer 2012, 12, 278-287
4. Flygare, J. A.; Pillow, T. H.; Aristoff, P. Antibody-Drug Conjugates for the Treatment of Cancer Chem. Biol. Drug Des. 2013, 81, 113-121
5. Adair, J. R.; Howard, P. W.; Hartley, J. A.; Williams, D. G.; Chester, K. A. Antibody-Drug Conjugates-A Perfect Synergy Expert Opin. Biol. Ther. 2012, 12, 1191-1206
6. Teicher, B. A.; Chari, R. V. J. Antibody Conjugate Therapeutics: Challenges and Potential Clin. Cancer Res. 2011, 17, 6389-6397
7. Sapra, P.; Hooper, A. T.; ODonnell, C. J.; Gerber, H.-P. Investigational Antibody Drug Conjugates for Solid Tumors Expert Opin. Invest. Drugs 2011, 20, 1131-1149
8. Polson, A. G.; Ho, W. Y.; Ramakrishnan, V. Investigational Antibody-Drug Conjugates for Hematological Malignancies Expert Opin. Invest. Drugs 2011, 20, 75-85
9. Alley, S. C.; Okeley, N. M.; Senter, P. D. Antibody-Drug Conjugates: Targeted Drug Delivery for Cancer Curr. Opin. Chem. Biol. 2010, 14, 529-537
10. Senter, P. D. Potent Antibody Drug Conjugates for Cancer Therapy Curr. Opin. Chem. Biol. 2009, 13, 235-244
11. Chari, R. V. J. Targeted Cancer Therapy: Conferring Specificity to Cytotoxic Drugs Acc. Chem. Res. 2008, 41, 98-107
12. Bross, P. F.; Beitz, J.; Chen, G.; Chen, X. H.; Duffy, E.; Kieffer, L.; Roy, S.; Sridhara, R.; Rahman, A.; Williams, G.; Pazdur, R. Approval Summary: Gemtuzumab Ozogamicin in Relapsed Acute Myeloid Leukemia Clin. Cancer Res. 2001, 7, 1490-1496
13. Katz, J.; Janik, J. E.; Younes, A. Brentuximab Vedotin (SGN-35) Clin. Cancer Res. 2011, 17, 6428-6436
14. Verma, S.; Miles, D.; Gianni, L.; Krop, I. E.; Welslau, M.; Baselga, J.; Pegram, M.; Oh, D.-Y.; Diéras, V.; Guardino, E.; Fang, L.; Lu, M. W.; Olsen, S.; Blackwell, K.; EMILIA Study Group. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer N. Engl. J. Med. 2012, 367, 1783-1791
15. Lewis Phillips, G. D.; Li, G.; Dugger, D. L.; Crocker, L. M.; Parsons, K. L.; Mai, E.; Blättler, W. A.; Lambert, J. M.; Chari, R. V. J.; Lutz, R. J.; Wong, W. L. T.; Jacobson, F. S.; Koeppen, H.; Schwall, R. H.; Kenkare-Mitra, S. R.; Spencer, S. D.; Sliwkowski, M. X. Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody-Cytotoxic Drug Conjugate Cancer Res. 2008, 68, 9280-9290
16. Wakankar, A. A.; Feeney, M. B.; Rivera, J.; Chen, Y.; Kim, M.; Sharma, V. K.; Wang, Y. J. Physicochemical Stability of the Antibody-Drug Conjugate Trastuzumab-DM1: Changes Due to Modification and Conjugation Processes Bioconjugate Chem. 2010, 21, 1588-1595
17. Junutula, J. R.; Flagella, K. M.; Graham, R. A.; Parsons, K. L.; Ha, E.; Raab, H.; Bhakta, S.; Nguyen, T.; Dugger, D. L.; Li, G.; Mai, E.; Lewis Phillips, G. D.; Hiraragi, H.; Fuji, R. N.; Tibbitts, J.; Vandlen, R.; Spencer, S. D.; Scheller, R. H.; Polakis, P.; Sliwkowski, M. X. Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Clin. Cancer Res. 2010, 16, 4769-4778
18. Junutula, J. R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D. D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S. P.; Dennis, M. S.; Lu, Y.; Meng, Y. G.; Ng, C.; Yang, J.; Lee, C. C.; Duenas, E.; Gorrell, J.; Katta, V.; Kim, A.; McDorman, K.; Flagella, K.; Venook, R.; Ross, S.; Spencer, S. D.; Lee Wong, W.; Lowman, H. B.; Vandlen, R.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Mallet, W. Site-Specific Conjugation of a Cytotoxic Drug to an Antibody Improves the Therapeutic Index Nat. Biotechnol. 2008, 26, 925-932
19. Ducry, L.; Stump, B. Antibody-Drug Conjugates: Linking Cytotoxic Payloads to Monoclonal Antibodies Bioconjugate Chem. 2010, 21, 5-13
20. Alley, S. C.; Benjamin, D. R.; Jeffrey, S. C.; Okeley, N. M.; Meyer, D. L.; Sanderson, R. J.; Senter, P. D. Contribution of Linker Stability to the Activities of Anticancer Immunoconjugates Bioconjugate Chem. 2008, 19, 759-765
21. Shen, B.-Q.; Xu, K.; Liu, L.; Raab, H.; Bhakta, S.; Kenrick, M.; Parsons-Reponte, K. L.; Tien, J.; Yu, S.-F.; Mai, E.; Li, D.; Tibbitts, J.; Baudys, J.; Saad, O. M.; Scales, S. J.; McDonald, P. J.; Hass, P. E.; Eigenbrot, C.; Nguyen, T.; Solis, W. A.; Fuji, R. N.; Flagella, K. M.; Patel, D.; Spencer, S. D.; Khawli, L. A.; Ebens, A.; Wong, W. L.; Vandlen, R.; Kaur, S.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Junutula, J. R. Conjugation Site Modulates the in Vivo Stability and Therapeutic Activity of Antibody-Drug Conjugates Nat. Biotechnol. 2012, 30, 184-189
22. Erickson, H. K.; Lewis Phillips, G. D.; Leipold, D. D.; Provenzano, C. A.; Mai, E.; Johnson, H. A.; Gunter, B.; Audette, C. A.; Gupta, M.; Pinkas, J.; Tibbitts, J. The Effect of Different Linkers on Target Cell Catabolism and Pharmacokinetics/Pharmacodynamics of Trastuzumab Maytansinoid Conjugates Mol. Cancer Ther. 2012, 11, 1133-1142
23. Poon, K. A.; Flagella, K.; Beyer, J.; Tibbitts, J.; Kaur, S.; Saad, O.; Yi, J.-H.; Girish, S.; Dybdal, N.; Reynolds, T. Preclinical Safety Profile of Trastuzumab Emtansine (T-DM1): Mechanism of Action of Its Cytotoxic Component Retained with Improved Tolerability Toxicol. Appl. Pharmacol. 2013, 273, 298-313
24. Krop, I. E.; Beeram, M.; Modi, S.; Jones, S. F.; Holden, S. N.; Yu, W.; Girish, S.; Tibbitts, J.; Yi, J.-H.; Sliwkowski, M. X.; Jacobson, F.; Lutzker, S. G.; Burris, H. A. 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. 2010, 28, 2698-2704
25. Girish, S.; Gupta, M.; Wang, B.; Lu, D.; Krop, I. E.; Vogel, C. L.; Burris Iii, H. A.; LoRusso, P. M.; Yi, J.-H.; Saad, O.; Tong, B.; Chu, Y.-W.; Holden, S.; Joshi, A. Clinical Pharmacology of Trastuzumab Emtansine (T-DM1): An Antibody-Drug Conjugate in Development for the Treatment of HER2-Positive Cancer Cancer Chemother. Pharmacol. 2012, 69, 1229-1240
26. Xu, K.; Liu, L.; Dere, R.; Mai, E.; Erickson, R.; Hendricks, A.; Lin, K.; Junutula, J. R.; Kaur, S. Characterization of the Drug-to-Antibody Ratio Distribution for Antibody-Drug Conjugates in Plasma/Serum Bioanalysis 2013, 5, 1057-1071
27. 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.; Chari, R. V. J. Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer J. Med. Chem. 2006, 49, 4392-4408
28. Cassady, J. M.; Chan, K. K.; Floss, H. G.; Leistner, E. Recent Developments in the Maytansinoid Antitumor Agents Chem. Pharm. Bull. 2004, 52, 1-26
29. Xu, K.; Liu, L.; Saad, O. M.; Baudys, J.; Williams, L.; Leipold, D.; Shen, B.; Raab, H.; Junutula, J. R.; Kim, A.; Kaur, S. Characterization of Intact Antibody-Drug Conjugates from Plasma/Serum in Vivo by Affinity Capture Capillary Liquid Chromatography-Mass Spectrometry Anal. Biochem. 2011, 412, 56-66
30. Dijkgraaf, G. J. P.; Alicke, B.; Weinmann, L.; Januario, T.; West, K.; Modrusan, Z.; Burdick, D.; Goldsmith, R.; Robarge, K.; Sutherlin, D.; Scales, S. J.; Gould, S. E.; Yauch, R. L.; de Sauvage, F. J. Small Molecule Inhibition of GDC-0449 Refractory Smoothened Mutants and Downstream Mechanisms of Drug Resistance Cancer Res. 2011, 71, 435-444
31. Pinheiro, P.; Bates, D.; DebRoy, S.; Sarkar, D.; R Development Core Team 2013. Nlme: Linear and Nonlinear Mixed Effects Models. R Package, version 3.1-108.
32. R Development Core Team 2012. R Package, version 3.1-110; R Foundation for Statistical Computing: Vienna, Austria, 2012.