Structural characterization of antibody drug conjugate by a combination of intact, middle-up and bottom-up techniques using sheathless capillary electrophoresis - Tandem mass spectrometry as nanoESI infusion platform and separation method

Analytica Chimica Acta

Volumn 918, Issue , 2016, Pages 50-59

  Said, Nassur ^a   Gahoual, Rabah ^a,b   Kuhn, Lauriane ^a   Beck, Alain ^c   François, Yannis Nicolas ^a   Leize Wagner, Emmanuelle ^a  

^a UNIVERSITÉ DE STRASBOURG   (France)

^b VU UNIVERSITY AMSTERDAM   (Netherlands)

^c INSTITUT DE RECHERCHE PIERRE FABRE   (France)

Author keywords

Antibody drug conjugate; Drug to antibody ratio; Drug loaded peptides; Sheathless capillary electrophoresis mass spectrometry; VcMMAE ADC

Indexed keywords

ANALOG TO DIGITAL CONVERSION; CAPILLARY ELECTROPHORESIS; CHARACTERIZATION; DRUG PRODUCTS; MASS SPECTROMETRY; MONOCLONAL ANTIBODIES; PEPTIDES; SPECTROMETRY;

ACCURATE MASS MEASUREMENTS; ANTIBODY-DRUG CONJUGATES; CAPILLARY ELECTROPHORESIS-MASS SPECTROMETRIES; DRUG TO ANTIBODY RATIO; PEPTIDE FRAGMENTATION; STRUCTURAL CHARACTERIZATION; TANDEM MASS SPECTROMETRY; VCMMAE-ADC;

ANTIBODIES;

ANTIBODY; ANTIBODY DRUG CONJUGATE; ASPARAGINE; BRENTUXIMAB VEDOTIN; GLUTAMYLTYROSYLLYSINE; GLYCINE; GLYCYLGLUTAMYLCYSTEINE; IMMUNOGLOBULIN F(AB')2 FRAGMENT; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN LIGHT CHAIN; LC FRAGMENT; POLYPEPTIDE; SERYLCYSTEINYLASPARTYLLYSINE; THREONYLHISTIDINYLTHREONYLCYSTEINYLPROPYLPROPYLCYSTEINYLPROPYLALANYLPROPYLGLUTAMYLLEUCYLLEUCYLGLYCINE; THREONYLLYSYLPHENYLALANYLARGINYLGLUTAMYLGLUTAMYLGLUTAMINYLTYROSYLASPARAGINYLSERYLTHREONYLTYROSYLARGININE; THREONYLLYSYLPROPYLARGINYLGLUTAMYLGLUTAMYLGLUTAMINYLTYROSYLASPARAGINYLSERYLTHREONYLTYROSYLARGININE; UNCLASSIFIED DRUG; ANTIBODY CONJUGATE;

ACCURACY; AMINO ACID SEQUENCE; ANTIBODY STRUCTURE; ARTICLE; CAPILLARY ELECTROPHORESIS; DRUG CONJUGATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; GLYCOSYLATION; HYDROPHOBICITY; INFUSION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; SEQUENCE ANALYSIS; SHEATHLESS CAPILLARY ELECTROPHORESIS-TANDEM MASS SPECTROMETRY; STRUCTURE ANALYSIS; TANDEM MASS SPECTROMETRY; CHEMISTRY; ELECTROSPRAY MASS SPECTROMETRY; PROCEDURES;

ELECTROPHORESIS, CAPILLARY; IMMUNOCONJUGATES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TANDEM MASS SPECTROMETRY;

EID: 84962815886     PISSN: 00032670     EISSN: 18734324     Source Type: Journal    
DOI: 10.1016/j.aca.2016.03.006     Document Type: Article

References (40)

1. Chari R.V.J. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Accounts Chem. Res. 2008, 41:98-107.
2. Ornes S. Antibody-drug conjugates. P. Natl. Acad. Sci. U. S. A. 2013, 110. 13695-13695.
3. Sapra P., Shor B. Monoclonal antibody-based therapies in cancer: advances and challenges. Pharmacol. Ther. 2013, 138:452-469.
4. Beck A., Reichert J.M. Antibody-drug conjugates. Mabs 2014, 6:15-17.
5. Zolot R.S., Basu S., Million R.P. Antibody-drug conjugates. Nat. Rev. Drug Discov. 2013, 12:259-260.
6. Beck A., Haeuw J.F., Wurch T., Goetsch L., Bailly C., Corvaia N. The next generation of antibody-drug conjugates comes of age. Discov. Med. 2010, 53:329-339.
7. Younes A., Bartlett N.L., Leonard J.P., Kennedy D.A., Lynch C.M., Sievers E.L., Forero-Torres A. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. New Engl. J. Med. 2010, 363:1812-1821.
8. Verma S., Miles D., Gianni L., Krop I.E., Welslau M., Baselga J., Pegram M., Oh D.Y., Dieras V., Guardino E., Fang L., Lu M.W., Olsen S., Blackwell K., Grp E.S. Trastuzumab emtansine for HER2-positive advanced breast cancer. New Engl. J. Med. 2012, 367:1783-1791.
9. Iyer U., Kadambi V.J. Antibody drug conjugates - trojan horses in the war on cancer. J. Pharmacol. Toxicol. Meth. 2011, 64:207-212.
10. Krapp S., Mimura Y., Jefferis R., Huber R., Sondermann P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J. Mol. Biol. 2003, 325:979-989.
11. Jefferis R. Recombinant antibody therapeutics: the impact of glycosylation on mechanisms of action. Trends Pharmacol. Sci. 2009, 30:356-362.
12. Beck A., Debaene F., Diemer H., Wagner-Rousset E., Colas O., Dorsselaer A.V., Cianférani S. Cutting-edge mass spectrometry characterization of originator, biosimilar and biobetter antibodies. J. Mass Spectrom. 2015, 50:285-297.
13. Biacchi M., Gahoual R., Said N., Beck A., Leize-Wagner E., François Y.-N. Glycoform separation and characterization of cetuximab variants by middle-up off-line capillary zone electrophoresis-UV/electrospray ionization-MS. Anal. Chem. 2015, 87:6240-6250.
14. Stoll D.R., Hannes D.C., Danforth J., Wagner E., Guillarme D., Fekete S., Beck A. Direct identification of rituximab main isoforms and subunit analysis by online selective comprehensive two-dimensional liquid chromatography-mass spectrometry. Anal. Chem. 2015, 87:8307-8315.
15. Debaene F., Boeuf A., Wagner-Rousset E., Colas O., Ayoub D., Corvaia N., Van Dorsselaer A., Beck A., Cianferani S. 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. 2014, 86:10674-10683.
16. François Y.-N., Biacchi M., Said N., Renard C., Beck A., Gahoual R., Leize-Wagner E. Characterization of cetuximab Fc/2 dimers by off-line CZE-MS. Anal. Chim. Acta 2016, 908:168-176.
17. Beck A., Wagner-Rousset E., Ayoub D., Van Dorsselaer A., Sanglier-Cianférani S. Characterization of therapeutic antibodies and related products. Anal. Chem. 2013, 85:715-736.
18. Janin-Bussat M.-C., 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 2015, 981:9-13.
19. Firth D., Bell L., Squires M., Estdale S., McKee C. A rapid approach for characterization of thiol-conjugated antibody-drug conjugates and calculation of drug-antibody ratio by liquid chromatography mass spectrometry. Anal. Biochem. 2015, 485:34-42.
20. Gahoual R., Busnel J.-M., Beck A., François Y.-N., Leize-Wagner E. Full antibody primary structure and microvariant characterization in a single injection using transient isotachophoresis and sheathless capillary electrophoresis-tandem mass spectrometry. Anal. Chem. 2014, 86:9074-9081.
21. Gahoual R., Biacchi M., Chicher J., Kuhn L., Hammann P., Beck A., Leize-Wagner E., Francois Y.N. Monoclonal antibodies biosimilarity assessment using transient isotachophoresis capillary zone electrophoresis-tandem mass spectrometry. Mabs 2014, 6:1464-1473.
22. Gahoual R., Beck A., François Y.-N., Leize-Wagner E. Independent highly sensitive characterization of asparagine deamidation and aspartic acid isomerization by sheathless CZE-ESI-MS/MS. J. Mass Spectrom. 2016, 51:150-158.
23. Francisco J.A., Cerveny C.G., Meyer D.L., Mixan B.J., Klussman K., Chace D.F., Rejniak S.X., Gordon K.A., DeBlanc R., Toki B.E., Law C.L., Doronina S.O., Siegall C.B., Senter P.D., Wahl A.F. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 2003, 102:1458-1465.
24. Oflazoglu E., Kissler K.M., Sievers E.L., Grewal I.S., Gerber H.P. Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in hodgkin lymphoma. Brit. J. Haematol. 2008, 142:69-73.
25. Valliere-Douglass J.F., McFee W.A., Salas-Solano O. Native intact mass determination of antibodies conjugated with monomethyl Auristatin E and F at interchain cysteine residues. Anal. Chem. 2012, 84:2843-2849.
26. Chen J., Yin S., Wu Y., Ouyang J. Development of a native nanoelectrospray mass spectrometry method for determination of the drug-to-antibody ratio of antibody-drug conjugates. Anal. Chem. 2013, 85:1699-1704.
27. Gahoual R., Busnel J.M., Wolff P., Francois Y.N., Leize-Wagner E. Novel sheathless CE-MS interface as an original and powerful infusion platform for nanoESI study: from intact proteins to high molecular mass noncovalent complexes. Anal. Bioanal. Chem. 2014, 406:1029-1038.
28. Wang B., Gucinski A.C., Keire D.A., Buhse L.F., Boyne M.T. Structural comparison of two anti-CD20 monoclonal antibody drug products using middle-down mass spectrometry. Analyst 2013, 138:3058-3065.
29. Zhang Z.Q., Pan H., Chen X.Y. mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom. Rev. 2009, 28:147-176.
30. Wakankar A., Chen Y., Gokarn Y., Jacobson F.S. Analytical methods for physicochemical characterization of antibody drug conjugates. mAbs 2011, 3:161-172.
31. Fekete S., Guillarme D., Sandra P., Sandra K. Chromatographic, electrophoretic, and mass spectrometric methods for the analytical characterization of protein biopharmaceuticals. Anal. Chem. 2016, 88(1):480-507.
32. Kalman-Szekeres Z., Olajos M., Ganzler K. Analytical aspects of biosimilarity issues of protein drugs. J. Pharm. Biomed. Anal. 2012, 69:185-195.
33. Fornelli L., Ayoub D., Aizikov K., Beck A., Tsybin Y.O. Middle-down analysis of monoclonal antibodies with electron transfer dissociation orbitrap fourier transform mass spectrometry. Anal. Chem. 2014, 86:3005-3012.
34. Beck A., Terral G., Debaene F., Wagner-Rousset E., Marcoux J., Janin-Bussat M.-C., Colas O., Van Dorsselaer A., Cianférani S. Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates. Expert Rev. Proteomics 2016, 13(2):157-183.
35. Resemann A., Jabs W., Wiechmann A., Wagner E., Colas O., Evers W., Belau E., Vorwerg L., Evans C., Beck A., Suckau D. Full validation of therapeutic antibody sequences by middle-up mass measurements and middle-down protein sequencing. mAbs 2016, 8(2):318-330.
36. Redman E.A., Mellors J.S., Starkey J.A., Ramsey J.M. Characterization of intact antibody drug conjugate variants using microfluidic capillary electrophoresis-mass spectrometry. Anal. Chem. 2016, 88(4):2220-2226.
37. 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. P. Natl. Acad. Sci. U. S. A. 2004, 101:17371-17376.
38. Flatman S., Alam I., Gerard J., Mussa N. Process analytics for purification of monoclonal antibodies. J. Chromatogr. B 2007, 848:79-87.
39. Gahoual R., Burr A., Busnel J.M., Kuhn L., Hammann P., Beck A., Franccois Y.N., Leize-Wagner E. Rapid and multi-level characterization of trastuzumab using sheathless capillary electrophoresis-tandem mass spectrometry. Mabs 2013, 5:479-490.
40. 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. Biotech. 2008, 26:925-932.