Analytical methods for physicochemical characterization of antibody drug conjugates

mAbs

Volumn 3, Issue 2, 2011, Pages 161-172

  Wakankar, Aditya ^b   Chen, Yan ^a   Gokarn, Yatin ^b   Jacobson, Fredric S ^a  

^a Protein Analytical Chemistry   (United States)

^b GENENTECH INC   (United States)

Author keywords

Analytical methods; Antibody drug conjugates; Auristatins; Biophysical characterization; Drug distribution; Drug loading; Drug to antibody ratio; Maytansines; Physicochemical characterization

Indexed keywords

CYTOTOXIC AGENT; DOXORUBICIN; MAYTANSINE; MONOCLONAL ANTIBODY; ANTIBODY CONJUGATE; DRUG;

ANALYTIC METHOD; CAPILLARY ELECTROPHORESIS; CONJUGATE; DRUG DISTRIBUTION; DRUG RELEASE; DRUG STABILITY; DRUG STRUCTURE; HYDROPHOBICITY; IMMUNOTHERAPY; MASS SPECTROMETRY; PEPTIDE MAPPING; REVIEW; CHEMICAL ANALYSIS; CHEMISTRY; CHROMATOGRAPHY; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOLOGY; METHODOLOGY;

ANTIBODIES, MONOCLONAL; CHEMISTRY TECHNIQUES, ANALYTICAL; CHROMATOGRAPHY; ELECTROPHORESIS, CAPILLARY; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOCONJUGATES; MASS SPECTROMETRY; PHARMACEUTICAL PREPARATIONS;

EID: 79952718320     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.3.2.14960     Document Type: Review

References (59)

1. Senter PD. Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 2009; 13:235-44.
2. Ranson M, Sliwkowski MX. Perspectives on anti-HER monoclonal antibodies. Oncology 2002; 63:17-24.
3. Morris PG, Fornier MN. Novel anti-tubulin cytotoxic agents for breast cancer. Expert Rev Anticancer Ther 2009; 9:175-85.
4. DiJoseph JF, Dougher MM, Armellino DC, Evans DY, Damle NK. Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia 2007; 21:2240-5. (Pubitemid 350011695)
5. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 2010; 363:1812-21.
6. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 2005; 23:1137-46. (Pubitemid 41486395)
7. Chari RV. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res 2008; 41:98-107.
8. Chari RV. Targeted delivery of chemotherapeutics: tumor-activated prodrug therapy. Adv Drug Deliv Rev 1998; 31:89-104. (Pubitemid 28191877)
9. Lambert JM. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol 2005; 5:543-9. (Pubitemid 41258574)
10. Payne G. Progress in immunoconjugate cancer therapeutics. Cancer Cell 2003; 3:207-12. (Pubitemid 37443876)
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. Sun MM, Beam KS, Cerveny CG, Hamblett KJ, Blackmore RS, Torgov MY, et al. Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides. Bioconjug Chem 2005; 16:1282-90. (Pubitemid 41368132)
13. McDonagh CF, Turcott E, Westendorf L, Webster JB, Alley SC, Kim K, et al. Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Protein Eng Des Sel 2006; 19:299-307. (Pubitemid 43999640)
14. Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD, Weir S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol 2008; 26:925-32.
15. Laguzza BC, Nichols CL, Briggs SL, Cullinan GJ, Johnson DA, Starling JJ, et al. New antitumor monoclonal antibody-vinca conjugates LY203725 and related compounds: design, preparation and representative in vivo activity. J Med Chem 1989; 32:548-55. (Pubitemid 19075702)
16. Chari RV, Martell BA, Gross JL, Cook SB, Shah SA, Blattler WA, et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res 1992; 52:127-31.
17. Hudecz F, Garnett MC, Khan T, Baldwin RW. The influence of synthetic conditions on the stability of methotrexate-monoclonal antibody conjugates determined by reversed phase high performance liquid chromatography. Biomed Chromatogr 1992; 6:128-32.
18. Chari RV, Jackel KA, Bourret LA, Derr SM, Tadayoni BM, Mattocks KM, et al. Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res 1995; 55:4079-84.
19. Greenfield RS, Kaneko T, Daues A, Edson MA, Fitzgerald KA, Olech LJ, et al. Evaluation in vitro of adriamycin immunoconjugates synthesized using an acid-sensitive hydrazone linker. Cancer Res 1990; 50:6600-7. (Pubitemid 20348786)
20. Willner D, Trail PA, Hofstead SJ, King HD, Lasch SJ, Braslawsky GR, et al. (6-Maleimidocaproyl)hydrazone of doxorubicin - a new derivative for the preparation of immunoconjugates of doxorubicin. Bioconjug Chem 1993; 4:521-7. (Pubitemid 2018209)
21. Hinman LM, Hamann PR, Wallace R, Menendez AT, Durr FE, Upeslacis J. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res 1993; 53:3336-42. (Pubitemid 23223306)
22. Moran J. Presentation at 224th American Chemical Society National Meeting, Boston, MA; August 18-22, 2002.
23. Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 2004; 10:7063-70. (Pubitemid 39383058)
24. Hamann PR, Hinman LM, Beyer CF, Lindh D, Upeslacis J, Flowers DA, et al. An anti-CD33 antibody- calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 2002; 13:40-6. (Pubitemid 34119633)
25. Siegel MM, Hollander IJ, Hamann PR, James JP, Hinman L, Smith BJ, et al. Matrix-assisted UV-laser desorption/ionization mass spectrometric analysis of monoclonal antibodies for the determination of carbohydrate, conjugated chelator and conjugated drug content. Anal Chem 1991; 63:2470-81.
26. Quiles S, Raisch KP, Sanford LL, Bonner JA, Safavy A. Synthesis and preliminary biological evaluation of high-drug-load paclitaxel-antibody conjugates for tumor-targeted chemotherapy. J Med Chem 2010; 53:586-94.
27. Safavy A, Bonner JA, Waksal HW, Buchsbaum DJ, Gillespie GY, Khazaeli MB, et al. Synthesis and biological evaluation of paclitaxel-C225 conjugate as a model for targeted drug delivery. Bioconjug Chem 2003; 14:302-10. (Pubitemid 36348653)
28. Sanderson RJ, Hering MA, James SF, Sun MM, Doronina SO, Siadak AW, et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res 2005; 11:843-52.
29. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 2003; 21:778-84. (Pubitemid 36791396)
30. Siegel MM, Tabei K, Kunz A, Hollander IJ, Hamann RR, Bell DH, et al. Calicheamicin derivatives conjugated to monoclonal antibodies: determination of loading values and distributions by infrared and UV matrix-assisted laser desorption/ionization mass spectrometry and electrospray ionization mass spectrometry. Anal Chem 1997; 69:2716-26.
31. Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, et al. 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; 16:4769-78.
32. 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 2005; 14:2436-46. (Pubitemid 41252812)
33. Lazar AC, Wang L, Blattler WA, Amphlett G, Lambert JM, Zhang W. Analysis of the composition of immunoconjugates using size-exclusion chromatography coupled to mass spectrometry. Rapid Commun Mass Spectrom 2005; 19:1806-14. (Pubitemid 40886704)
34. Lazar AC, Krishnamurthy R. Evaluation of the effect of sample composition and sample load on the mass spectrometric analysis of immunoconjugates, TPY403, at the Proceedings of the 55th American Society for Mass Spectrometry Annual Conference on Mass Spectrometry and Allied Topics, Indianapolis, Indiana June 3-7, 2007.
35. Stephan JP, Chan P, Lee C, Nelson C, Elliott JM, Bechtel C, et al. Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on pharmacokinetic parameters determination. Bioconjug Chem 2008; 19:1673-83.
36. Kunz A. 2004. Calicheamycin derivative carrier conjugates, United States Patent Application Publication, No. US 2004/01929200 A1.
37. Stan AC, Radu DL, Casares S, Bona CA, Brumeanu TD. Antineoplastic efficacy of doxorubicin enzymatically assembled on galactose residues of a monoclonal antibody specific for the carcinoembryonic antigen. Cancer Res 1999; 59:115-21. (Pubitemid 29062966)
38. Rosenberg AS, Worobec A. A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 1: Considering consequences of the immune response to a protein. Biopharm Intl 2004; 19:22-6.
39. Rosenberg AS, Worobec A. A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 2: Considering host-specific and product-specific factors impacting immunogenicity. Biopharm Intl 2004; 19:34-42.
40. Hollander I, Kunz A, Hamann PR. Selection of reaction additives used in the preparation of monomeric antibody-calicheamicin conjugates. Bioconjug Chem 2008; 19:358-61. (Pubitemid 351213870)
41. King HD, Dubowchik GM, Mastalerz H, Willner D, Hofstead SJ, Firestone RA, et al. Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: inhibition of aggregation by methoxytriethyleneglycol chains. J Med Chem 2002; 45:4336-43. (Pubitemid 35025579)
42. Cordoba AJ, Shyong BJ, Breen D, Harris RJ. Nonenzymatic hinge region fragmentation of antibodies in solution. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 818:115-21. (Pubitemid 40331815)
43. Hunt G, Nashabeh W. Capillary electrophoresis sodium dodecyl sulfate nongel sieving analysis of a therapeutic recombinant monoclonal antibody: a biotechnology perspective. Anal Chem 1999; 71:2390-7. (Pubitemid 29307602)
44. Liu J, Abid S, Lee MS. Analysis of monoclonal antibody chimeric BR96-doxorubicin immunoconjugate by sodium dodecyl sulfate-capillary gel electrophoresis with ultraviolet and laser-induced fluorescence detection. Anal Biochem 1995; 229:221-8.
45. Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, et al. Charge variants in IgG1: Isolation, characterization, in vitro binding properties and pharmacokinetics in rats. mAbs 2010; 2.
46. Harris RJ, Kabakoff B, Macchi FD, Shen FJ, Kwong M, Andya JD, et al. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B Biomed Sci Appl 2001; 752:233-45. (Pubitemid 32168159)
47. Vlasak J, Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr Pharm Biotechnol 2008; 9:468-81.
48. Maeda E, Urakami K, Shimura K, Kinoshita M, Kakehi K. Charge heterogeneity of a therapeutic monoclonal antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin. J Chromatogr A 2010; 1217:7164-71.
49. Liu J, Zhao H, Volk KJ, Klohr SE, Kerns EH, Lee MS. Analysis of monoclonal antibody and immunoconjugate digests by capillary electrophoresis and capillary liquid chromatography. J Chromatogr A 1996; 735:357-66. (Pubitemid 26202393)
50. Sosic Z, Houde D, Blum A, Carlage T, Lyubarskaya Y. Application of imaging capillary IEF for characterization and quantitative analysis of recombinant protein charge heterogeneity. Electrophoresis 2008; 29:4368-76.
51. 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.
52. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 2003; 102:1458-65. (Pubitemid 36988057)
53. Fleming MS, Zhang W, Lambert JM, Amphlett G. A reversed-phase high-performance liquid chromatography method for analysis of monoclonal antibody-maytansinoid immunoconjugates. Anal Biochem 2005; 340:272-8. (Pubitemid 40544866)
54. Hurwitz E, Levy R, Maron R, Wilchek M, Arnon R, Sela M. The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Cancer Res 1975; 35:1175-81.
55. Law CL. 2010. Anti-CD70 antibody-drug conjugates and their use for the treatment of cancer and immune disorders. US patent no 7,662,387 B2.
56. 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. (Pubitemid 43157592)
57. Wakankar AA, Feeney MB, Rivera J, Chen Y, Kim M, Sharma VK, et al. Physicochemical stability of the antibody-drug conjugate trastuzumab-DM1: changes due to modification and conjugation processes. Bioconjug Chem 2010; 21:1588-95.
58. Rathore AS, Mhatre R, Eds. Quality by design for biopharmaceuticals: Principles and case studies. Hoboken, NJ: John Wiley & Sons, Inc 2009.
59. Goetze AM, Schenauer MR, Flynn GC. Assessing monoclonal antibody product quality attribute criticality through clinical studies. mAbs 2:500-7.