Advertisement

The AAPS Journal

, 21:101 | Cite as

Comparison of Bevacizumab Quantification Results in Plasma of Non-small Cell Lung Cancer Patients Using Bioanalytical Techniques Between LC-MS/MS, ELISA, and Microfluidic-based Immunoassay

  • Noriko Iwamoto
  • Megumi Takanashi
  • Takashi ShimadaEmail author
  • Jiichiro Sasaki
  • Akinobu HamadaEmail author
Research Article

Abstract

The development of analytical techniques to study therapeutic monoclonal antibodies is expected to be useful for pharmacokinetic analysis and for the development of therapeutic indexes to determine dosage standards. To date, the blood concentration of antibody drugs has been analyzed by the enzyme-linked immunosorbent assay (ELISA). However, with the development of mass spectrometry and microfluidization technologies, the assay implication is drastically changing. We have developed an analytical validation method for many monoclonal antibodies and Fc-fusion proteins using Fab-selective proteolysis nSMOL coupled with liquid chromatography-mass spectrometry (LC-MS/MS). However, the correlation between the analyzed data characterization and the referable value from individual measurement techniques has not been adequately discussed. Therefore, in this study, we discussed in detail the relationship of the bioanalytical data from three different techniques, LC-MS/MS, ELISA, and microfluidic immunoassay, using 245 clinical plasma samples from non-small cell lung cancer patients treated with bevacizumab. The quantified concentration data of bevacizumab in human plasma indicated that the results obtained were almost the same correlation regardless of which technique was used. And the referable value from LC-MS/MS and microfluidic immunoassay were similar and correlated compared with ELISA.

KEY WORDS

bevacizumab bioanalysis ELISA LC-MS microfluidic immunoassay nSMOL 

Notes

Acknowledgements

This study of the LBA-based assay was performed by Dr. Naoe Yamane of CMIC Pharma Science (Tokyo, Japan).

Compliance with Ethical Standards

This study was reviewed and approved by the relevant institutional review boards and signed informed consent was obtained from all patients prior to participation. The procedures were in accordance with the Helsinki Declaration.

Supplementary material

12248_2019_369_MOESM1_ESM.docx (33 kb)
ESM 1 (DOCX 33 kb)

References

  1. 1.
    Chen SC, Quartino A, Polhamus D, Riggs M, French J, Wang X, et al. Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with >/=2 HER2-targeted regimens. Br J Clin Pharmacol. 2017;83(12):2767–77.  https://doi.org/10.1111/bcp.13381.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Geukes Foppen MH, Rozeman EA, van Wilpe S, Postma C, Snaebjornsson P, van Thienen JV, et al. Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management. ESMO Open. 2018;3(1):e000278.  https://doi.org/10.1136/esmoopen-2017-000278.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Nishidate M, Hayashi M, Aikawa H, Tanaka K, Nakada N, Miura SI, et al. Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development. Drug Metab Pharmacokinet. 2019;34:209–16.  https://doi.org/10.1016/j.dmpk.2019.04.006.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu X, Lukowski JK, Flinders C, Kim S, Georgiadis RA, Mumenthaler SM, et al. MALDI-MSI of immunotherapy: mapping the EGFR-targeting antibody Cetuximab in 3D colon-cancer cell cultures. Anal Chem. 2018;90(24):14156–64.  https://doi.org/10.1021/acs.analchem.8b02151. CrossRefPubMedGoogle Scholar
  5. 5.
    Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D, et al. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nat Commun. 2018;9(1):4904.  https://doi.org/10.1038/s41467-018-07334-3.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Roussey JA, Viglianti SP, Teitz-Tennenbaum S, Olszewski MA, Osterholzer JJ. Anti-PD-1 antibody treatment promotes clearance of persistent Cryptococcal lung infection in mice. J Immunol. 2017;199(10):3535–46.  https://doi.org/10.4049/jimmunol.1700840.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lee CH, Romain G, Yan W, Watanabe M, Charab W, Todorova B, et al. IgG Fc domains that bind C1q but not effector Fcgamma receptors delineate the importance of complement-mediated effector functions. Nat Immunol. 2017;18(8):889–98.  https://doi.org/10.1038/ni.3770.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, et al. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011;17(19):6304–12.  https://doi.org/10.1158/1078-0432.CCR-10-3336.CrossRefPubMedGoogle Scholar
  9. 9.
    Saito M, Kawakami Y, Yamashita K, Nasuno H, Ishimine YU, Fukuda K, et al. HER2-positive gastric cancer identified by serum HER2: a case report. Oncol Lett. 2016;11(6):3575–8.  https://doi.org/10.3892/ol.2016.4470.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, et al. Exposure-response analyses of Ramucirumab from two randomized, phase III trials of second-line treatment for advanced gastric or gastroesophageal junction cancer. Mol Cancer Ther. 2017;16(10):2215–22.  https://doi.org/10.1158/1535-7163.MCT-16-0895.CrossRefPubMedGoogle Scholar
  11. 11.
    Shah N, Mohammad AS, Saralkar P, Sprowls SA, Vickers SD, John D, et al. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol Res. 2018;132:47–68.  https://doi.org/10.1016/j.phrs.2018.03.021.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Li M, Kroetz DL. Bevacizumab-induced hypertension: clinical presentation and molecular understanding. Pharmacol Ther. 2018;182:152–60.  https://doi.org/10.1016/j.pharmthera.2017.08.012.CrossRefPubMedGoogle Scholar
  13. 13.
    Baker JHE, Kyle AH, Reinsberg SA, Moosvi F, Patrick HM, Cran J, et al. Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment. Clin Exp Metastasis. 2018;35(7):691–705.  https://doi.org/10.1007/s10585-018-9929-3.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhao X, Suryawanshi S, Hruska M, Feng Y, Wang X, Shen J, et al. Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors. Ann Oncol. 2017;28(8):2002–8.  https://doi.org/10.1093/annonc/mdx235.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Iwamoto N, Shimada T, Umino Y, Aoki C, Aoki Y, Sato TA, et al. Selective detection of complementarity-determining regions of monoclonal antibody by limiting protease access to the substrate: nano-surface and molecular-orientation limited proteolysis. Analyst. 2014;139(3):576–80.  https://doi.org/10.1039/c3an02104a.CrossRefPubMedGoogle Scholar
  16. 16.
    Cruz E, Kayser V. Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics. 2019;13:33–51.  https://doi.org/10.2147/BTT.S166310.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yang Z, Hayes M, Fang X, Daley MP, Ettenberg S, Tse FL. LC-MS/MS approach for quantification of therapeutic proteins in plasma using a protein internal standard and 2D-solid-phase extraction cleanup. Anal Chem. 2007;79(24):9294–301.  https://doi.org/10.1021/ac0712502.CrossRefPubMedGoogle Scholar
  18. 18.
    Gong C, Zheng N, Zeng J, Aubry AF, Arnold ME. Post-pellet-digestion precipitation and solid phase extraction: a practical and efficient workflow to extract surrogate peptides for ultra-high performance liquid chromatography--tandem mass spectrometry bioanalysis of a therapeutic antibody in the low ng/mL range. J Chromatogr A. 2015;1424:27–36.  https://doi.org/10.1016/j.chroma.2015.10.049.CrossRefPubMedGoogle Scholar
  19. 19.
    Iwamoto N, Shimada T, Terakado H, Hamada A. Validated LC-MS/MS analysis of immune checkpoint inhibitor Nivolumab in human plasma using a Fab peptide-selective quantitation method: nano-surface and molecular-orientation limited (nSMOL) proteolysis. J Chromatogr B Anal Technol Biomed Life Sci. 2016;1023-1024:9–16.  https://doi.org/10.1016/j.jchromb.2016.04.038.CrossRefGoogle Scholar
  20. 20.
    Iwamoto N, Umino Y, Aoki C, Yamane N, Hamada A, Shimada T. Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano-surface and molecular-orientation limited (nSMOL) proteolysis. Drug Metab Pharmacokinet. 2016;31(1):46–50.  https://doi.org/10.1016/j.dmpk.2015.11.004.CrossRefPubMedGoogle Scholar
  21. 21.
    Iwamoto N, Shimada T. Recent advances in mass spectrometry-based approaches for proteomics and biologics: great contribution for developing therapeutic antibodies. Pharmacol Ther. 2018;185:147–54.  https://doi.org/10.1016/j.pharmthera.2017.12.007.CrossRefPubMedGoogle Scholar
  22. 22.
    Honda N, Lindberg U, Andersson P, Hoffmann S, Takei H. Simultaneous multiple immunoassays in a compact disc-shaped microfluidic device based on centrifugal force. Clin Chem. 2005;51(10):1955–61.  https://doi.org/10.1373/clinchem.2005.053348.CrossRefPubMedGoogle Scholar
  23. 23.
    Myzithras M, Bigwarfe T, Waltz E, Li H, Ahlberg J, Rybina I, et al. Optimizing NBE PK/PD assays using the Gyrolab Affinity Software; conveniently within the bioanalyst's existing workflow. Bioanalysis. 2018;10(6):397–406.  https://doi.org/10.4155/bio-2017-0251.CrossRefPubMedGoogle Scholar
  24. 24.
    Pohl G, Shih Ie M. Principle and applications of digital PCR. Expert Rev Mol Diagn. 2004;4(1):41–7.CrossRefGoogle Scholar
  25. 25.
    Nishio K, Gokon N, Hasegawa M, Ogura Y, Ikeda M, Narimatsu H, et al. Identification of a chemical substructure that is immobilized to ferrite nanoparticles (FP). Colloids Surf B: Biointerfaces. 2007;54(2):249–53.  https://doi.org/10.1016/j.colsurfb.2006.10.039.CrossRefPubMedGoogle Scholar
  26. 26.
    Iwamoto N, Hamada A, Shimada T. Antibody drug quantitation in coexistence with anti-drug antibodies on nSMOL bioanalysis. Anal Biochem. 2018;540-541:30–7.  https://doi.org/10.1016/j.ab.2017.11.002.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Leading Technology of Bioanalysis and Protein ChemistryShimadzu CorporationKyotoJapan
  2. 2.Shimadzu Bioscience Research PartnershipShimadzu Scientific InstrumentsBothellUSA
  3. 3.Research and Development Center for New Medical FrontiersKitasato University School of MedicineSagamiharaJapan
  4. 4.Division of Molecular PharmacologyNational Cancer Center Research InstituteTokyoJapan
  5. 5.Department of Pharmacology and Therapeutics, Fundamental Innovative Oncology CoreNational Cancer Center Research InstituteTokyoJapan
  6. 6.Division of Clinical Pharmacology and Translational Research, Exploratory Oncology Research & Clinical Trial CenterNational Cancer CenterTokyoJapan

Personalised recommendations