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Review

The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review)

  • Authors:
    • Tomislav Laptoš
    • Jasna Omersel
  • View Affiliations / Copyright

    Affiliations: Pharmacy Unit, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia, Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
  • Pages: 3161-3168
    |
    Published online on: January 31, 2018
       https://doi.org/10.3892/etm.2018.5821
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Abstract

The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino‑acid moieties. With increasing use of medicinal products that contain mAbs, and their self‑administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance. This review summarises the correct handling of mAb biologicals from the point of view of the pharmacist, clinical biochemist and patient, as is supported by relevant cases from the literature and our own data and experience. In particular, if there is a break in the cold chain, both healthcare professionals and patients need to be aware of the potential pharmacokinetics and pharmacodynamics alterations to these biologicals. Furthermore, any alterations in the protein structure can induce harmful immune reactions, including anaphylaxis and cytokine storms, or result in the production of neutralising or blocking Abs. Overall, considering also that treatment costs usually remain high, drug stability can have a tremendous effect on the clinical, humanistic and economic outcomes of such treatments.
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1 

Das G and Rees A: Use of monoclonal antibodies for proprotein convertase subtilisin kexin type 9 inhibition: Issues with efficacy, tolerability and safety. Curr Opin Lipidol. 25:96–98. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Elvin JG, Couston RG and van der Walle CF: Therapeutic antibodies: Market considerations, disease targets and bioprocessing. Int J Pharm. 440:83–98. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Shukla D, Schneider CP and Trout BL: Molecular level insight into intra-solvent interaction effects on protein stability and aggregation. Adv Drug Deliv Rev. 63:1074–1085. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Wang W: Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 185:129–188. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Berrill A, Biddlecombe J and Bracewell D: Product quality during manufacture and supplyPeptide and protein delivery. Chris Van Der W: Academic Press; Boston, MA: pp. 313–339. 2011, View Article : Google Scholar

6 

Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR and Volkin DB: Protein-excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev. 63:1118–1159. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Bee JS, Nelson SA, Freund E, Carpenter JF and Randolph TW: Precipitation of a monoclonal antibody by soluble tungsten. J Pharm Sci. 98:3290–3301. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Davies MJ: The oxidative environment and protein damage. Biochim Biophys Acta. 1703:93–109. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Margiloff L, Chaplia L, Chow A, Singhal PC and Mattana J: Metal-catalyzed oxidation of immunoglobulin G impairs Fc receptor-mediated binding to macrophages. Free Radic Biol Med. 25:780–785. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Liu D, Ren D, Huang H, Dankberg J, Rosenfeld R, Cocco MJ, Li L, Brems DN and Remmele RL Jr: Structure and stability changes of human IgG1 Fc as a consequence of methionine oxidation. Biochemistry. 47:5088–5100. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Mian IS, Bradwell AR and Olson AJ: Structure, function and properties of antibody binding sites. J Mol Biol. 217:133–151. 1991. View Article : Google Scholar : PubMed/NCBI

12 

Dimitrov JD, Ivanovska ND, Lacroix-Desmazes S, Doltchinkova VR, Kaveri SV and Vassilev TL: Ferrous ions and reactive oxygen species increase antigen-binding and anti-inflammatory activities of immunoglobulin G. J Biol Chem. 281:439–446. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Omersel J, Jurgec I, Cucnik S, Kveder T, Rozman B, Sodin-Semrl S and Bozic B: Autoimmune and proinflammatory activity of oxidized immunoglobulins. Autoimmun Rev. 7:523–529. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Daugherty AL and Mrsny RJ: Formulation and delivery issues for monoclonal antibody therapeutics. Adv Drug Deliv Rev. 58:686–706. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Huang L, Lu J, Wroblewski VJ, Beals JM and Riggin RM: In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem. 77:1432–1439. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Vermeer AW and Norde W: The thermal stability of immunoglobulin: Unfolding and aggregation of a multi-domain protein. Biophys J. 78:394–404. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Liu H, Gaza-Bulseco G and Sun J: Characterization of the stability of a fully human monoclonal IgG after prolonged incubation at elevated temperature. J Chromatogr B Analyt Technol Biomed Life Sci. 837:35–43. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Ye H: Simultaneous determination of protein aggregation, degradation, and absolute molecular weight by size exclusion chromatography-multiangle laser light scattering. Anal Biochem. 356:76–85. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Segura A, Herrera M, González E, Vargas M, Solano G, Gutiérrez JM and León G: Stability of equine IgG antivenoms obtained by caprylic acid precipitation: Towards a liquid formulation stable at tropical room temperature. Toxicon. 53:609–615. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Arakawa T, Prestrelski SJ, Kenney WC and Carpenter JF: Factors affecting short-term and long-term stabilities of proteins. Adv Drug Deliv Rev. 46:307–326. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Wang W, Nema S and Teagarden D: Protein aggregation-pathways and influencing factors. Int J Pharm. 390:89–99. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Hawe A, Kasper JC, Friess W and Jiskoot W: Structural properties of monoclonal antibody aggregates induced by freeze-thawing and thermal stress. Eur J Pharm Sci. 38:79–87. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Wang W: Lyophilization and development of solid protein pharmaceuticals. Int J Pharm. 203:1–60. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Chang BS, Kendrick BS and Carpenter JF: Surface-induced denaturation of proteins during freezing and its inhibition by surfactants. J Pharm Sci. 85:1325–1330. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Cleland JL and Langer R: Formulation and Delivery of Proteins and Peptides: Design and Development Strategies. (ACS Symposium Series 567). American Chemical Society; Washington, DC: 1994, View Article : Google Scholar

26 

Hermeling S, Crommelin DJ, Schellekens H and Jiskoot W: Structure-immunogenicity relationships of therapeutic proteins. Pharm Res. 21:897–903. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Rosenberg AS: Effects of protein aggregates: An immunologic perspective. AAPS J. 8:E501–E507. 2006. View Article : Google Scholar : PubMed/NCBI

28 

De Groot AS and Scott DW: Immunogenicity of protein therapeutics. Trends Immunol. 28:482–490. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Keiserman M, Codreanu C, Handa R, Xibillé-Friedmann D, Mysler E, Briceño F and Akar S: The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: Practical consequences. Expert Rev Clin Immunol. 10:1049–1057. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Schellekens H and Jiskoot W: Eprex-associated pure red cell aplasia and leachates. Nat Biotechnol. 24:613–614. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD and Panoskaltsis N: Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 355:1018–1028. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Hwang WY and Foote J: Immunogenicity of engineered antibodies. Methods. 36:3–10. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Joubert MK, Hokom M, Eakin C, Zhou L, Deshpande M, Baker MP, Goletz TJ, Kerwin BA, Chirmule N, Narhi LO and Jawa V: Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses. J Biol Chem. 287:25266–25279. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Brinks V, Jiskoot W and Schellekens H: Immunogenicity of therapeutic proteins: The use of animal models. Pharm Res. 28:2379–2385. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Swanson SJ and Bussiere J: Immunogenicity assessment in non-clinical studies. Curr Opin Microbiol. 15:337–347. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Breckenridge A: Report of the working party on the addition of drugs to intravenous infusion fluids (HC(76)9). Department of Health and Social Security; London: 1976

37 

Langford S, Fradgley S, Evans M and Blanks C: Assessing the risk of handling monoclonal antibodies. Hospital Pharm. 15:60–64. 2008.

38 

Odou P: Medical devices for safe handling of cytotoxic drugs. Eur J Oncol Pharm. 4:17–19. 2010.

39 

Paul M, Vieillard V, Jaccoulet E and Astier A: Long-term stability of diluted solutions of the monoclonal antibody rituximab. Int J Pharm. 436:282–290. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Grundstein A, Meentemeyer V and Dowd J: Maximum vehicle cabin temperatures under different meteorological conditions. Int J Biometeorol. 53:255–261. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Laguerre O and Flick D: Temperature prediction in domestic refrigerators: Deterministic and stochastic approaches. Int J Refrigeration. 33:41–51. 2010. View Article : Google Scholar

42 

James SJ, Evans J and James C: A review of the performance of domestic refrigerators. J Food Eng. 87:2–10. 2008. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Laptoš T and Omersel J: The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review). Exp Ther Med 15: 3161-3168, 2018.
APA
Laptoš, T., & Omersel, J. (2018). The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review). Experimental and Therapeutic Medicine, 15, 3161-3168. https://doi.org/10.3892/etm.2018.5821
MLA
Laptoš, T., Omersel, J."The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review)". Experimental and Therapeutic Medicine 15.4 (2018): 3161-3168.
Chicago
Laptoš, T., Omersel, J."The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review)". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3161-3168. https://doi.org/10.3892/etm.2018.5821
Copy and paste a formatted citation
x
Spandidos Publications style
Laptoš T and Omersel J: The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review). Exp Ther Med 15: 3161-3168, 2018.
APA
Laptoš, T., & Omersel, J. (2018). The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review). Experimental and Therapeutic Medicine, 15, 3161-3168. https://doi.org/10.3892/etm.2018.5821
MLA
Laptoš, T., Omersel, J."The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review)". Experimental and Therapeutic Medicine 15.4 (2018): 3161-3168.
Chicago
Laptoš, T., Omersel, J."The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review)". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3161-3168. https://doi.org/10.3892/etm.2018.5821
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