Antibody-drug conjugate bioanalysis using LB-LC-MS/MS hybrid assays: Strategies, methodology and correlation to ligand-binding assays

Bioanalysis

Volumn 8, Issue 13, 2016, Pages 1383-1401

  Wang, Jian ^a   Gu, Huidong ^a   Liu, Ang ^a   Kozhich, Alexander ^a   Rangan, Vangipuram ^b   Myler, Heather ^a   Luo, Linlin ^a   Wong, Richard ^a   Sun, Huadong ^a   Wang, Bonnie ^a   Vezina, Heather E ^a   Deshpande, Shrikant ^b   Zhang, Yan ^a   Yang, Zheng ^a   Olah, Timothy V ^a   Aubry, Anne Francoise ^a   Arnold, Mark E ^a   Pillutla, Renuka ^a   Desilva, Binodh ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b Biologics Discovery California   (United States)

Author keywords

antibody conjugated payload; antibody drug conjugate; DAR bias; DAR sensitive ADC assay; drug antibody ratio; fit for purpose bioanalysis; generic reagents; immunocapture LC MS MS hybrid assay; ligand binding LC MS MS hybrid assay; soluble target

Indexed keywords

ANTIBODY DRUG CONJUGATE; ANTIBODY IDIOTYPE CONJUGATE; ANTIBODY PAYLOAD CONJUGATE; CATHEPSIN B; CHEMICAL COMPOUND; GENERIC REAGENT; PROTEIN A; PROTEIN G; TRYPSIN; UNCLASSIFIED DRUG; ANTIBODY CONJUGATE; DRUG;

ANALYTIC METHOD; ARTICLE; CONCENTRATION (PARAMETERS); CORRELATIONAL STUDY; DRUG TO ANTIBODY RATIO; ENZYME METABOLISM; FIT FOR PURPOSE BIOANALYSIS; LIGAND BINDING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PHARMACOLOGICAL PARAMETERS; ANIMAL; BLOOD; HAPLORHINI; HUMAN; IMMUNOASSAY; LIMIT OF DETECTION; PROCEDURES; RAT; TANDEM MASS SPECTROMETRY;

ANIMALS; CHROMATOGRAPHY, LIQUID; HAPLORHINI; HUMANS; IMMUNOASSAY; IMMUNOCONJUGATES; LIMIT OF DETECTION; PHARMACEUTICAL PREPARATIONS; RATS; TANDEM MASS SPECTROMETRY;

EID: 84975507115     PISSN: 17576180     EISSN: 17576199     Source Type: Journal    
DOI: 10.4155/bio-2016-0017     Document Type: Article

References (59)

1. US FDA. FDA approves Adcetris to treat two types of lymphoma (2011). www.fda.gov
2. US FDA. FDA approves new treatment for late-stage breast cancer (2013). www.fda.gov
3. Goldmacher V, Kovtun Y. Antibody-drug conjugates: using monoclonal antibodies for delivery of cytotoxic payloads to cancer cells. Ther. Deliv. 2(3), 397-416 (2011
4. Perez HL, Cardarelli PM, Deshpande S, et al. Antibody-drug conjugates: current status and future directions. Drug Discov. Today 19(7), 869-881 (2013
5. Beck A, Reichert JM. Antibody-drug conjugates: present and future. MAbs 6, 15-17 (2014
6. Mullard A. Maturing antibody-drug conjugate pipeline hits 30. Nat. Rev. Drug Discov. 12, 329-332 (2013
7. Kaur S. Bioanalysis special focus issue on antibody-drug conjugates. Bioanalysis 5(9), 981-983 (2013
8. Gorovits B. Bioanlaysis of antibody-drug conjugates. Bioanalysis 7(13), 1559-1560 (2015
9. Gorovits B, Alley SC, Bilic S, et al. 2011 Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper. Bioanalysis 5(9), 997-1006 (2013
10. Kaur S, Xu K, Saad OM, et al. Bioanalytical assay strategies for the development of antibody-drug conjugate biotherapeutics. Bioanalysis 5(2), 201-226 (2013
11. Stephan JP, Kozak KR, Wong WL. Challenges in developing bioanalytical assays for characterization of antibody-drug conjugates. Bioanalysis 3(6), 677-700 (2011
12. Sauerborn M, Dongen W. Practical considerations for the pharmacokinetic and immunogenic assessment of antibody-drug conjugates. Biodrugs 28, 383-391 (2014
13. Clark T, Han X, King L, et al. Insights into antibody-drug conjugates: bioanalysis and biomeasures in discovery. Bioanalysis 5(9), 985-987 (2013
14. Tumey LN, Rago B, Han X. In vivo biotransformation of antibody-drug conjugates. Bioanalysis 7(13), 1649-1664 (2015
15. Saad OM, Shen BQ, Xu K, et al. Bioanalytical approaches for characterizing catabolism of antibody-drug conjugates. Bioanalysis 7(13), 1583-1604 (2015
16. Kraynov E, Kamath AV, Walles M, et al. Current approaches for ADME characterization of antibody-drug conjugates: an industry White Paper. Drug Metab. Dispos. 44(5), 617-623 (2015
17. Tibbitts J, Canter D, Graff R, Smith A, Khawli LA. Key factors influencing ADME properties of therapeutic proteins: a need for ADME characterization in drug discovery and development. MAbs 8(2), 229-45 (2016
18. Beck A, Terral G, Debaene F, et al. Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates. Expert Rev. Proteomics 13(2), 157-183 (2016
19. Kumar S, King LE, Clark TH. Antibody-drug conjugates nonclinical support: from early to late nonclinical bioanalysis using ligand-binding assays. Bioanalysis 7(13), 1605-1617 (2015
20. Myler H, Rangan VS, Kozhich A, et al. Validaiton of an integrated series of ligand binding assays for the quantitative determination of antibody drug conjugate in biological matrices. Bioanalysis 8(6), 519-531 (2016
21. Myler H, Rangan VS, Wang J, et al. An integrated multiplatform bioanalytical strategy for antibody-drug conjugates: a novel case study. Bioanalysis. 7(13), 1569-1582 (2015
22. 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
23. Lin K, Tibbitts J. Pharmacokinetic consideration for antibody drug conjugates. Pharm. Res. 29, 2354-2366 (2012
24. Shah D, Barletta F, Betts A, et al. Key bioanalytical measurements for antibody-drug conjugate development: PK/PD modelers perspective. Bioanalysis 5(9), 989-992 (2013
25. Bender B, Leipold DD, Xu K, et al. A mechanistic pharmacokinetic model elucidating the disposition of trasutuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) for treatment of metastatic breast cancer. AAPS J. 16(5), 994-1008 (2014
26. Sukumaran S, Gadkar K, Zhang C, et al. Mechanismbased pharmacokinetic/pharmacodynamic model for THIOMAB™ drug conjugates. Pharm Res. 32(6), 1884-1893 (2014
27. Khot A, Sharma S, Shah D. Integration of bioanalytical measurements using PK-PD modeling and simulation: implications for antibody-drug conjugate development. Bioanalysis 7(13), 1633-1648 (2015
28. Stephan JP, Chan P, Lee C, et al. Anti-CD22-MCC-DM1 and MC-MMAF conjuagtes: impact of assay formation on pharmacokinetic parameters determination. Bioconj. Chem. 19, 1673-1683 (2008
29. 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, 56-66 (2011
30. 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
31. Luo Q, Chung HH, Borths C, et al. Structural characterization of a monoclonal antibody-maytansinoid immunoconjugate. Anal. Chem. 88(1), 695-702 (2016
32. Redman EA, Mellors JS, Starkey JA, Ramsey JM. Characterization of intact antibody drug conjugate variants using microfluidic CE-MS. Anal. Chem. 88(4), 2220-2226 (2016
33. Liu A, Kozhich A, Passmore D, et al. Quantitative bioanalysis of antibody-conjugated payload in monkey plasma using a hybrid immuno-capture LC-MS/MS approach: assay development, validation, and a case study. J. Chromatogr. B 1002, 54-62 (2015
34. Sanderson RJ, Nicholas ND, Baker Lee C, et al. Antibodyconjugated drug assay for protease-cleavable antibody-drug conjugates. Bioanalysis 8(1), 55-63 (2016
35. Birdsall RE, McCarthy SM, Janin-Bussat MC, et al. A sensitive multidimensional method for the detection, characterization, and quantification of trace free drug species in antibody-drug conjugate samples using mass spectral detection. MAbs 8(2), 306-317 (2016
36. Li Y, Gu C, Gruenhagen J, Yehl P, Chetwyn NP, Medley CD. An enzymatic deconjugation method for the analysis of small molecule active drugs on antibody-drug conjugates. MAbs 8(4), 698-705 (2016
37. Heudi O, Barteau S, Picard F, Kretz O. Quantitative analysis of maytansinoid (DM1) in human serum by on-line solid phase extraction coupled with liquid chromatography tandem mass spectrometry -Method validation and its application to clinical samples. J. Pharm. Biomed. Anal. 120, 322-332 (2016
38. Neubert H, Muirhead D, Kabir M, et al. Sequential protein and peptide immunoaffinity capture for mass spectrometrybased quantification of total human β-nerve growth factor. Anal. Chem. 85, 1719-1726 (2013
39. Lund H, Lovsletten K, Paus E, et al. Immuno-MS based targeted proteomics: highly specific sensitive and reproducible human chorionic gonadotropin determination for clinical diagnostics and doping analysis. Anal. Chem. 84, 7926-7932 (2012
40. Whiteaker JR, Zhao L, Zhang HY, et al. Antibody-based enrichment of peptides on magnetic beads for massspectrometry-based quantification of serum biomarkers. Anal. Biochem. 362, 44-54 (2007
41. Schlosser G, Vekey K, Malorni A, et al. Combination of solid-phase affinity capture on paramagnetic beads and mass spectrometry to study non-covalent interactions: example of minor groove binding drugs. Rapid Commun. Mass Spectrom. 19, 3307-3314 (2005
42. 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, & regulatory agencies input). Bioanalysis 6(23), 3237-3249 (2014
43. Knutsson M, Schmidt R. LC-MS/MS of large molecules in a regulated bioanalytical enviroment-which acceptance criteria to apply. Bioanalysis 5(18), 2211-2214(2013
44. DeSilva B, Smith W, Weiner R, et al. Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules. Pharm. Res. 20, 1885-1900 (2003
45. Duggan JX, Vazvaei F, Jenkins R. Bioanalytical method validation considerations for LC-MS/MS assays of therapeutic proteins. Bioanalysis 7(11), 1389-1395 (2015
46. Jenkins R, Duggan JX, Aubry AF, et al. Recommendations for validation of LC-MS/MS bioanalytical methods for protein biotherapeutics. AAPS J. 17(1), 1-16 (2015
47. Rao C, Rangan VS, Deshpande S. Challenges in antibody-drug conjugate discovery: a bioconjugation and analytical perspective, Bioanalysis 7(13), 1561-1564 (2015
48. Lee JW. Generic method approaches for monoclonal antibody therapeutics analysis using both ligand binding and LC-MS/MS techniques. Bioanalysis 8(1), 19-27 (2016
49. Lee JM, Kelley M, King LE, et al. Bioanalytical approaches to quantify total and free therapeutic antibodies and their targets: technical challenges and PK/PD applications over the course of drug development. AAPS J. 13, 99-110 (2011
50. Mayer AP, Hottenstein CS. Ligand-binding assay development: what do you want to measure versus what you are measuring? AAPS J. 18(2), 287-289 (2015
51. 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
52. 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
53. Tumey LN, Charati M, He T, et al. Mild method for succinimide hydrolysis on ADCs: impact on ADC potency, stability, exposure, and efficacy. Bioconjug. Chem. 25(10), 1871-1880 (2014
54. US Department of Health and Human Services, Food Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry: Bioanalytical Method Validation. Rockville, MD, USA (2013). www.fda.gov
55. European Medicines Agency. Guideline on Bioanalytical Method Validation. London, UK (2011). www.ema.europa.eu
56. Japan Ministry of Health and Labor Welfare. Guideline on Bioanalytical Method (Ligand Binding Assay) Validation in Pharmaceutical Development (2014
57. China Pharmacopoeia (ChP). Draft Guidance on Bioanalytical Method Validation (2014). http://knex2014.europeanbioanalysisforum.eu
58. Vangipuram SR, Myler H, Kozhich A, et al. Biotransformation and stability of antibody-drug conjugates: payload metabolism and linker cleavage delineation. Bioanalysis 7(11), 1319-1323 (2015
59. Wada R, Erickson HK, Lewis Phillips GD, et al. Mechanistic pharmacokinetic/pharmacodynamic modeling of in vivo tumor uptake, catabolism, and tumor response of trastuzumab maytansinoid conjugates. Cancer Chemother. Pharmacol. 74(5), 969-980 (2014