Bioanalytical approaches for characterizing catabolism of antibody-drug conjugates

Bioanalysis

Volumn 7, Issue 13, 2015, Pages 1583-1604

  Saad, Ola M ^a   Shen, Ben Quan ^a   Xu, Keyang ^a   Khojasteh, S Cyrus ^a   Girish, Sandhya ^a   Kaur, Surinder ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY DRUG CONJUGATE; CYTOTOXIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR 2; MONOCLONAL ANTIBODY; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; VEDOTIN; ANTIBODY CONJUGATE;

BIOTRANSFORMATION; BREAST METASTASIS; CONJUGATION; DRUG ACCUMULATION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG METABOLISM; HUMAN; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; PEPTIDE MAPPING; REVIEW; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; WHOLE BODY AUTORADIOGRAPHY; BIOASSAY; IMMUNOLOGY; METABOLISM;

ANTIBODIES, MONOCLONAL; BIOLOGICAL ASSAY; HUMANS; IMMUNOCONJUGATES; METABOLISM;

EID: 84938317077     PISSN: 17576180     EISSN: 17576199     Source Type: Journal    
DOI: 10.4155/bio.15.87     Document Type: Review

References (78)

1. Strebhardt K, Ullrich A. Paul Ehrlichs magic bullet concept: 100 years of progress. Nat. Rev. Cancer 8(6), 473-480 (2008
2. Flygare JA, Pillow TH, Aristoff P. Antibody-drug conjugates for the treatment of cancer. Chem. Biol. Drug Des. 81(1), 113-121 (2013
3. Beck A, Reichert JM. Antibody-drug conjugates: present and future. MAbs 6(1), 15-17 (2014
4. Bross PF, Beitz J, Chen G et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7(6), 1490-1496 (2001
5. Larson RA, Sievers EL, Stadtmauer EA et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104(7), 1442-1452 (2005
6. Sievers EL, Larson RA, Stadtmauer EA et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33- positive acute myeloid leukemia in first relapse. J. Clin. Oncol. 19(13), 3244-3254 (2001
7. De Claro RA, Mcginn K, Kwitkowski V et al. U.S. Food and Drug Administration approval summary: brentuximab vedotin for the treatment of relapsed hodgkin lymphoma or relapsed systemic anaplastic large-cell lymphoma. Clin. Cancer Res. 18(21), 5845-5849 (2012
8. Amiri-Kordestani L, Blumenthal GM, Xu QC et al. FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin. Cancer Res. 20(17), 4436-4441 (2014
9. Mullard A. Maturing antibody-drug conjugate pipeline hits. Nat. Rev. Drug Discov. 12(5), 329-332 (2013).
10. Saber H, Leighton JK. An FDA oncology analysis of antibody-drug conjugates. Regul. Toxicol. Pharmacol. 71(3), 444-452 (2015
11. Huskey SE, Li W, Mangold JB, Flarakos J. An industry perspective on tiered approach to the investigation of metabolites in drug development. Bioanalysis 6(5), 617-628 (2014
12. Vugmeyster Y, Harrold J, Xu X. Absorption, distribution, metabolism, and excretion (ADME) studies of biotherapeutics for autoimmune and inflammatory conditions. AAPS J. 14(4), 714-727 (2012
13. Vugmeyster Y, Xu X, Theil FP, Khawli LA, Leach MW. Pharmacokinetics and toxicology of therapeutic proteins: advances and challenges. World J. Biol. Chem. 3(4), 73-92 (2012
14. Xu X, Vugmeyster Y. Challenges and opportunities in absorption, distribution, metabolism, and excretion studies of therapeutic biologics. AAPS J. 14(4), 781-791 (2012
15. Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J. Pharm. Sci. 93(11), 2645-2668 (2004
16. Sands H, Jones PL. Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor. J. Nucl. Med. 28(3), 390-398 (1987
17. Boswell CA, Mundo EE, Zhang C et al. Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-STEAP1 antibody-drug conjugates in rats. Bioconjug. Chem. 22(10), 1994-2004 (2011
18. Boswell CA, Tesar DB, Mukhyala K, Theil FP, Fielder PJ, Khawli LA. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug. Chem. 21(12), 2153-2163 (2010
19. Kamath AV, Iyer S. Challenges and advances in the assessment of the disposition of antibody drug conjugates. Biopharm Drug Dispos doi: 10.1002/bdd.1957 (2015) (Epub ahead of print
20. Han TH, Zhao B. Absorption, distribution, metabolism, and excretion considerations for the development of antibody-drug conjugates. Drug Metab. Dispos. 42(11), 1914-1920 (2014
21. Gorovits B, Alley SC, Bilic S et al. Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-drug Conjugate Working Group position paper. Bioanalysis 5(9), 997-1006 (2013
22. Kaur S, Xu K, Saad OM, Dere RC, Carrasco-Triguero M. Bioanalytical assay strategies for the development of antibody-drug conjugate biotherapeutics. Bioanalysis 5(2), 201-226 (2013
23. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat. Biotechnol. 23(9), 1137-1146 (2005
24. Nolting B. Linker technologies for antibody-drug conjugates. Methods Mol. Biol. 1045, 71-100 (2013
25. Junutula JR, Raab H, Clark S et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 26(8), 925-932 (2008
26. Behrens CR, Liu B. Methods for site-specific drug conjugation to antibodies. MAbs 6(1), 46-53 (2014
27. Drake PM, Albers AE, Baker J et al. Aldehyde tag coupled with HIPS chemistry enables the production of ADCs conjugated site-specifically to different antibody regions with distinct in vivo efficacy and PK outcomes. Bioconjug. Chem. 25(7), 1331-1341 (2014
28. Bernardes GJ, Steiner M, Hartmann I, Neri D, Casi G. Sitespecific chemical modification of antibody fragments using traceless cleavable linkers. Nat. Protoc. 8(11), 2079-2089 (2013
29. Panowksi S, Bhakta S, Raab H, Polakis P, Junutula JR. Sitespecific antibody drug conjugates for cancer therapy. MAbs 6(1), 34-45 (2014
30. Beck A, Lambert J, Sun M, Lin K. Fourth world antibody-drug conjugate summit: February 29-March 1, 2012 Frankfurt, Germany. MAbs 4(6), 637-647 (2012
31. Kellner C, Bleeker WK, Lammerts Van Bueren JJ et al. Human kappa light chain targeted Pseudomonas exotoxin A-identifying human antibodies and Fab fragments with favorable characteristics for antibody-drug conjugate development. J. Immunol. Methods 371(1-2), 122-133 (2011
32. Berger EA. Targeted cytotoxic therapy: adapting a rapidly progressing anticancer paradigm for depletion of persistent HIV-infected cell reservoirs. Curr. Opin. HIV AIDS 6(1), 80-85 (2011
33. Verma VA, Pillow TH, Depalatis L et al. The cryptophycins as potent payloads for antibody drug conjugates. Bioorg. Med. Chem. Lett. 25(4), 864-868 (2015
34. Dere R, Yi JH, Lei C et al. PK assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine. Bioanalysis 5(9), 1025-1040 (2013
35. Dufield D, Neubert H, Garofolo F et al. 2014 white paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 2 - hybrid LBA/LCMS, ELN and regulatory agencies input). Bioanalysis 6(23), 3237-3249 (2014
36. Lebert D, Picard G, Beau-Larvor C et al. Absolute and multiplex quantification of antibodies in serum using PSAQ standards and LC-MS/MS. Bioanalysis 1-15 (2015
37. Boswell CA, Mundo EE, Firestein R et al. An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2. Br. J. Pharmacol. 168(2), 445-457 (2013
38. Cohen R, Vugts DJ, Visser GW et al. Development of novel ADCs: Conjugation of tubulysin analogues to trastuzumab monitored by dual radiolabeling. Cancer Res. 74(20), 5700-5710 (2014
39. Xu K, Liu L, Saad OM et al. Characterization of intact antibody-drug conjugates from plasma/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry. Anal. Biochem. 412(1), 56-66 (2011
40. Debaene F, Boeuf A, Wagner-Rousset E et al. Innovative native MS methodologies for antibody drug conjugate characterization: high resolution native MS and IM-MS for average DAR and DAR distribution assessment. Anal. Chem. 86(21), 10674-10683 (2014
41. Marcoux J, Champion T, Colas O et al. Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate. Protein Sci. doi:10.1002/pro.2666 (2015) (Epub ahead of print
42. Vincents B, Von Pawel-Rammingen U, Bjorck L, Abrahamson M. Enzymatic characterization of the streptococcal endopeptidase, IdeS, reveals that it is a cysteine protease with strict specificity for IgG cleavage due to exosite binding. Biochemistry 43(49), 15540-15549 (2004
43. Von Pawel-Rammingen U, Johansson BP, Bjorck L. IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J. 21(7), 1607-1615 (2002
44. Wagner-Rousset E, Janin-Bussat MC, Colas O et al. Antibody-drug conjugate model fast characterization by LCMS following ides proteolytic digestion. MAbs 6(1), 173-184 (2014
45. Wenig K, Chatwell L, Von Pawel-Rammingen U, Bjorck L, Huber R, Sondermann P. Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG. Proc. Natl Acad. Sci. USA 101(50), 17371-17376 (2004
46. Xu K, Liu L, Dere R et al. Characterization of the drug-toantibody ratio distribution for antibody-drug conjugates in plasma/serum. Bioanalysis 5(9), 1057-1071 (2013
47. Yang Y, Strahan A, Li C et al. Detecting low level sequence variants in recombinant monoclonal antibodies. MAbs 2(3), 285-298 (2010
48. Beck A, Wagner-Rousset E, Ayoub D, Van Dorsselaer A, Sanglier-Cianferani S. Characterization of therapeutic antibodies and related products. Anal. Chem. 85(2), 715-736 (2013
49. Udeshi ND, Mertins P, Svinkina T, Carr SA. Large-scale identification of ubiquitination sites by mass spectrometry. Nat. Protoc. 8(10), 1950-1960 (2013
50. Wang L, Amphlett G, Blattler WA, Lambert JM, Zhang W. Structural characterization of the maytansinoid-monoclonal antibody immunoconjugate, huN901-DM1, by mass spectrometry. Protein Sci. 14(9), 2436-2446 (2005
51. Rosati S, Van Den Bremer ET, Schuurman J, Parren PW, Kamerling JP, Heck AJ. In-depth qualitative and quantitative analysis of composite glycosylation profiles and other micro-heterogeneity on intact monoclonal antibodies by high-resolution native mass spectrometry using a modified Orbitrap. MAbs 5(6), 917-924 (2013
52. Janin-Bussat MC, Dillenbourg M, Corvaia N, Beck A, Klinguer-Hamour C. Characterization of antibody drug conjugate positional isomers at cysteine residues by peptide mapping LC-MS analysis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 981-982, 9-13 (2015
53. Bongers J, Cummings JJ, Ebert MB et al. Validation of a peptide mapping method for a therapeutic monoclonal antibody: what could we possibly learn about a method we have run 100 times? J. Pharm. Biomed. Anal. 21(6), 1099-1128 (2000
54. Venable JD, Dong MQ, Wohlschlegel J, Dillin A, Yates JR. Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra. Nat. Methods 1(1), 39-45 (2004
55. Gillet LC, Navarro P, Tate S et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol. Cell. Proteomics 11(6), O111.016717 (2012
56. Fan TW, Lorkiewicz PK, Sellers K, Moseley HN, Higashi RM, Lane AN. Stable isotope-resolved metabolomics and applications for drug development. Pharmacol. Ther. 133(3), 366-391 (2012
57. Clarke NJ, Rindgen D, Korfmacher WA, Cox KA. Systematic LC/MS metabolite identification in drug discovery. Anal. Chem. 73(15), 430A-439A (2001
58. Zhang H, Zhu M, Ray KL, Ma L, Zhang D. Mass defect profiles of biological matrices and the general applicability of mass defect filtering for metabolite detection. Rapid Commun. Mass Spectrom. 22(13), 2082-2088 (2008
59. Zhu M, Ma L, Zhang D et al. Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data. Drug Metab. Dispos. 34(10), 1722-1733 (2006
60. Shen BQ, Xu K, Liu L et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat. Biotechnol. 30(2), 184-189 (2012
61. Kaur S, Xu K, Saad O, Liu L, Slattery T, Dere R. Mass spectrometry of antibody-drug conjugates in plasma and tissue in drug development. In:Characterization of Protein Therapeutics Using Mass Spectrometry. Chen G (Ed.). Springer, NY, USA, 279-304 (2013
62. Alley SC, Benjamin DR, Jeffrey SC et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug. Chem. 19(3), 759-765 (2008
63. Shearer TW, Smith KS, Diaz D, Asher C, Ramirez J. The role of in vitro ADME assays in antimalarial drug discovery and development. Comb. Chem. High Throughput Screen. 8(1), 89-98 (2005
64. Penner N, Xu L, Prakash C. Radiolabeled absorption, distribution, metabolism, and excretion studies in drug development: why, when, and how? Chem. Res. Toxicol. 25(3), 513-531 (2012
65. Heikkinen AT, Lignet F, Cutler P, Parrott N. The role of quantitative ADME proteomics to support construction of physiologically-based pharmacokinetic models for use in small molecule drug development. Proteomics Clin. Appl. doi:10.1002/prca.201400147 (2015) (Epub ahead of print
66. Shen BQ, Bumbaca D, Saad O et al. Catabolic fate and pharmacokinetic characterization of trastuzumab emtansine (T-DM1): An emphasis on preclinical and clinical catabolism. Curr. Drug Metab. 13(7), 901-910 (2012
67. Wong S, Bumbaca D, Yue Q et al. Nonclinical disposition, metabolism, and in vitro drug-drug interaction assessment of DM1, a component of trastuzumab emtansine (T-DM1). Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2011. San Francisco, CA, USA, 12-16 November 2011.
68. Boswell CA, Mundo EE, Zhang C et al. Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-STEAP1 antibody-drug conjugates in rats. Bioconjug. Chem. 22(10), 1994-2004 (2011
69. Erickson HK, Park PU, Widdison WC et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 66(8), 4426-4433 (2006
70. Alley SC, Zhang X, Okeley NM et al. The pharmacologic basis for antibody-auristatin conjugate activity. J. Pharmacol. Exp. Ther. 330(3), 932-938 (2009
71. Shen B-Q, Bumbaca D, Yue Q et al. Non-clinical disposition and metabolism of DM1, a component of trastuzumab emtansine (T-DM1), in sprague dawley rats. Drug Metabol. Lett. (2015)(In press
72. Erickson HK, Lewis Phillips GD, Leipold DD et al. The effect of different linkers on target cell catabolism and pharmacokinetics/pharmacodynamics of trastuzumab maytansinoid conjugates. Mol. Cancer Ther. 11(5), 1133-1142 (2012
73. Widdison W, Wilhelm S, Veale K et al. Metabolites of antibody-maytansinoid conjugates: characteristics and in vitro potencies. Mol. Pharm. 12 (6) 1762-1773 (2015
74. Uppal H, Doudement E, Mahapatra K et al. Potential mechanisms for thrombocytopenia development with trastuzumab emtansine (T-DM1). Clin. Cancer Res. 21(1), 123-133 (2015
75. Wang H, Rangan VS, Sung MC et al. Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody- drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans. Biopharm. Drug Dispos. doi:10.1002/bdd.1953 (2015)(Epub ahead of print
76. Foo HC, Smith NW, Stanley SM. Fabrication of an on-line enzyme micro-reactor coupled to liquid chromatographytandem mass spectrometry for the digestion of recombinant human erythropoietin. Talanta 135, 18-22 (2015
77. Camerini S, Mauri P. The role of protein and peptide separation before mass spectrometry analysis in clinical proteomics. J. Chromatogr. A 1381, 1-12 (2015
78. Dueker SR, Lohstroh PN, Giacomo JA, Le TV, Keck BD, Vogel JS. Early human ADME using microdoses and microtracers: bioanalytical considerations. Bioanalysis 2(3), 441-454 (2010