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Therapeutic Antibodies

  • Karen M. Nagel
Chapter
Part of the AAPS Introductions in the Pharmaceutical Sciences book series (AAPSINSTR)

Abstract

Monoclonal antibodies are the most rapidly growing area of drug research and development. Their ability to target certain cell surface antigens has been advantageous in cancer and transplant therapy, though many early, mouse-derived products had limited long-term use due to the potential for immunogenicity. Advances in recombinant technology and the ability to make antibodies less immunogenic by making them more human have led to routine use in chronic conditions as well. While all products currently marketed are injectable, a number of those targeted at autoimmune conditions such as rheumatoid arthritis, psoriasis, and related conditions are available in easy-to-use self-injection systems.

Keywords

Monoclonal antibodies Human anti-mouse antibodies Human anti-chimeric antibodies Human anti-human antibodies Neutralizing antibodies Monoclonal antibody nomenclature Antibody fragments Antibody conjugates Fusion proteins Bispecific antibodies Adverse effects of monoclonal antibodies 

References

  1. 1.
    Nagel K, Karash A. Biotechnology. In: Desai A, Lee M, editors. Gibaldi's drug delivery systems in pharmaceutical care New American Society of HealthSystems Pharmacists. New York: American Society of Health System’s Pharmacists; 2007.Google Scholar
  2. 2.
    Chan CE, Chan AH, Hanson BJ, Ooi EE. The use of antibodies in the treatment of infectious diseases. Singapore Med J. 2009;50(7):663-72; quiz 73.Google Scholar
  3. 3.
    Nagel KM. Monoclonal antibody therapeutics. KeePosted 2004;31(9 SRC - BaiduScholar):25–39.Google Scholar
  4. 4.
    Drlica K. Beyond the central dogma: a sampling from the insights derived from gene cloning. Understanding DNA and gene cloning: a guide for the curious. 4th ed. Newark: Wiley; 2004.Google Scholar
  5. 5.
    Drug Facts and Comparisons Secondary Drug Facts and Comparisons 2018. http://www.lww.com/Product/9781574393705.
  6. 6.
    FDA. FDA Center for Biologics Evaluation and Research Website. Secondary FDA Center for Biologics Evaluation and Research Website. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133072.htm.
  7. 7.
    Daly BJ LCaC, D. Snakebite treatment and management. http://emedicine.medscape.com/article/168828-treatment.
  8. 8.
    Anand B, Deng R, Theil FP, et al. Monoclonal antibodies: from structure to therapeutic application. In: Crommelin DJA SRaMB, editor. Pharmaceutical biotechnology: fundamentals and applications. 3rd ed. New York: Informa Healthcare; 2008.Google Scholar
  9. 9.
    Brooks G. Monoclonal antibodies as therapeutic agents. In: Biotechnology in healthcare: an introduction to biopharmaceuticals. London: Pharmaceutical Press; 1998.Google Scholar
  10. 10.
    Pandit N. Biopharmaceuticals. In: Introduction to the pharmaceuticals sciences. Baltimore: Lippincott Williams & Wilkens; 2007.Google Scholar
  11. 11.
    Motofolio: scientific illustration toolkits for presentations and publications. Secondary Motofolio: scientific illustration toolkits for presentations and publications. http://www.motifolio.com.
  12. 12.
    Li J, Zhu Z. Research and development of next generation of antibody-based therapeutics. Acta Pharmacol Sin. 2010;31(9):1198–207.  https://doi.org/10.1038/aps.2010.120. [published Online First: Epub Date].CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Middaugh CR, Siahann TJ. Pharmaceutical biotechnology. In: Sinko P, editor. Martin’s physical pharmacy and pharmaceutical sciences. 6th ed. Baltimore: Lippincott Williams & Wilkins; 2011.Google Scholar
  14. 14.
    Kubota T, Niwa R, Satoh M, Akinaga S, Shitara K, Hanai N. Engineered therapeutic antibodies with improved effector functions. Cancer Sci. 2009;100(9):1566–72.  https://doi.org/10.1111/j.1349-7006.2009.01222.x. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  15. 15.
    Kaneko E, Niwa R. Optimizing therapeutic antibody function: progress with Fc domain engineering. BioDrugs. 2011;25(1):1–11.  https://doi.org/10.2165/11537830-000000000-00000. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  16. 16.
    Campbell J, Lowe D, Sleeman MA. Developing the next generation of monoclonal antibodies for the treatment of rheumatoid arthritis. Br J Pharmacol. 2011;162(7):1470–84.  https://doi.org/10.1111/j.1476-5381.2010.01183.x. [published Online First: Epub Date].CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ricart AD. Immunoconjugates against solid tumors: mind the gap. Clin Pharmacol Ther. 2011;89(4):513–23.  https://doi.org/10.1038/clpt.2011.8. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  18. 18.
    Genetics S. Brentuximab package insert. Secondary Brentuximab package insert. http://www.seattlegenetics.com/application/files/1915/2157/0234/adcetris_USPI.pdf.
  19. 19.
    Casi G, Neri D. Antibody-drug conjugates and small molecule-drug conjugates: opportunities and challenges for the development of selective anticancer cytotoxic agents. J Med Chem. 2015;58(22):8751–61.  https://doi.org/10.1021/acs.jmedchem.5b00457. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  20. 20.
    Fagete S, Fischer N. Smarter drugs: a focus on pan-specific monoclonal antibodies. BioDrugs. 2011;25(6):357–64.  https://doi.org/10.2165/11594690-000000000-00000. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  21. 21.
    Muller D, Kontermann RE. Bispecific antibodies for cancer immunotherapy: current perspectives. BioDrugs. 2010;24(2):89–98.  https://doi.org/10.2165/11530960-000000000-00000. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  22. 22.
    Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–58.  https://doi.org/10.1038/clpt.2008.170. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  23. 23.
    Lin K, Tibbitts J. Pharmacokinetic considerations for antibody drug conjugates. Pharm Res. 2012;29(9):2354–66.  https://doi.org/10.1007/s11095-012-0800-y. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  24. 24.
    Rowland MTT. Protein drugs. clinical pharmacokinetics and pharmacodynamics: concepts and applications. 4th ed. Baltimore: Lippincott Williams & Wilkins; 2011.Google Scholar
  25. 25.
    Mould DR, Sweeney KR. The pharmacokinetics and pharmacodynamics of monoclonal antibodies--mechanistic modeling applied to drug development. Curr Opin Drug Discov Devel. 2007;10(1):84–96.PubMedGoogle Scholar
  26. 26.
    Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93(11):2645–68.  https://doi.org/10.1002/jps.20178. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  27. 27.
    Weimert NA, Alloway RR. Monoclonal antibodies in solid organ transplantation. In: Sindelar RD, Meibohm BE, editors. Pharmaceutical biotechnology: fundamentals and applications. 3rd ed. New York: Informa Healthcare; 2008.Google Scholar
  28. 28.
    Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs. 2010;14(2):E10–21.  https://doi.org/10.1188/10.cjon.e10-e21. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  29. 29.
    Kulkarni HS, Kasi PM. Rituximab and cytokine release syndrome. Case Rep Oncol. 2012;5(1):134–41.  https://doi.org/10.1159/000337577. [published Online First: Epub Date].CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325–38.  https://doi.org/10.1038/nrd3003. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  31. 31.
    Seminara NM, Gelfand JM. Assessing long-term drug safety: lessons (re) learned from raptiva. Semin Cutan Med Surg. 2010;29(1):16–9.  https://doi.org/10.1016/j.sder.2010.01.001. [published Online First: Epub Date].CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Bohra C, Sokol L, Dalia S. Progressive multifocal leukoencephalopathy and monoclonal antibodies: a review. Cancer Control. 2017;24(4):1073274817729901.  https://doi.org/10.1177/1073274817729901. [published Online First: Epub Date].CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Keene DL, Legare C, Taylor E, Gallivan J, Cawthorn GM, Vu D. Monoclonal antibodies and progressive multifocal leukoencephalopathy. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2011;38(4):565–71.Google Scholar
  34. 34.
    Molloy ES. PML and rheumatology: the contribution of disease and drugs. Cleve Clin J Med. 2011;78(Suppl 2):S28–32.  https://doi.org/10.3949/ccjm.78.s2.07. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  35. 35.
    Comi G. Natalizumab: state of the art and open questions. Neurol Sci. 2011;31(Suppl 3):313–5.  https://doi.org/10.1007/s10072-010-0430-2. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  36. 36.
    Duddy M, Haghikia A, Cocco E, et al. Managing MS in a changing treatment landscape. J Neurol. 2011;258(5):728–39.  https://doi.org/10.1007/s00415-011-6009-x. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  37. 37.
    Harris JM, Kuebler P, Panzara MA. Monoclonal antibodies in anti-inflammatory therapy. In: Crommelin DJA, Sindelar RD, Meibohm B, editors. Pharmaceutical biotechnology: fundamentals and applications. 3rd ed. New York: Informa Healthcare; 2008.Google Scholar
  38. 38.
    Biogen. Tysabri touch website. Secondary Tysabri touch website. http://www.tysabri.com/safety-with-tysabri.xml.
  39. 39.
    Nagel K, Karash A. Oncologic disorders. In: Desai A, Lee M, editors. Gibaldis drug delivery systems in pharmaceutical care New American Society of HealthSystems Pharmacists. New York: American Society of Health System's Pharmacists; 2007.Google Scholar
  40. 40.
    Ho RJY, Gibaldi M. Enzymes. In: Ho RJY, Gibaldi M, editors. Biotechnology and biopharmaceuticals: transforming proteins and genes into drugs. Hoboken: Wiley-Liss; 2003.CrossRefGoogle Scholar
  41. 41.
    Kuth JC, Jones TS, Hanje J, Moroney SEM. Monoclonal antibodies in cancer. In: Sindelar RD, Meibohm BE, editors. Pharmaceutical biotechnology: fundamentals and applications. 3rd ed. New York: Informa Healthcare; 2008.Google Scholar
  42. 42.
    Prasad V. The withdrawal of drugs for commercial reasons: the incomplete story of tositumomab. JAMA Intern Med. 2014;174(12):1887–8.  https://doi.org/10.1001/jamainternmed.2014.5756. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  43. 43.
    Kline GS. Bexxar package insert. Secondary Bexxar package insert 2012. http://us.gsk.com/products/assets/us_bexxar.pdf.
  44. 44.
    Spectrum. Zevalin package insert. Secondary Zevalin package insert 2012. http://www.zevalin.com/wp-content/uploads/2012/03/Zevalin_Package_Insert.pdf.
  45. 45.
    Astellas. Letter to patients on Amevive product discontinuation. Secondary Letter to patients on Amevive product discontinuation 2012. http://www.amevive.com/Patient%20letter.pdf.
  46. 46.
    Foundation A Information on ease-of-use product selection. Secondary Information on ease-of-use product selection 2012. http://www.arthritis.org/ease-of-use-new.php?ct_id=5.
  47. 47.
    International nonproprietary names (INN) for biological and biotechnological substances (a review). 2012, 17 SRC - BaiduScholar. http://www.who.int/medicines/services/inn/BioRev2011.pdf. Accessed 17 Sept 2012.
  48. 48.
    Yazdi MH, Faramarzi MA, Nikfar S, Falavarjani KG, Abdollahi M. Ranibizumab and aflibercept for the treatment of wet age-related macular degeneration. Expert Opin Biol Ther. 2015;15(9):1349–58.  https://doi.org/10.1517/14712598.2015.1057565. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  49. 49.
    Genentech. Xolair package insert. Secondary Xolair package insert 2012. http://www.gene.com/gene/products/information/pdf/xolair-prescribing.pdf.
  50. 50.
    Medimmune. Synagis package insert. Secondary Synagis package insert 2012. http://www.medimmune.com/pdf/products/synagis_pi.pdf.
  51. 51.
    Giovannoni G, Gold R, Selmaj K, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial. Lancet Neurol. 2014;13(5):472–81.  https://doi.org/10.1016/s1474-4422(14)70039-0. [published Online First: Epub Date].CrossRefPubMedGoogle Scholar
  52. 52.
    Daclizumab withdrawn from the market worldwide. Drug Ther Bull. 2018;56(4):38.  https://doi.org/10.1136/dtb.2018.4.0604. [published Online First: Epub Date].

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Karen M. Nagel
    • 1
  1. 1.Chicago College of PharmacyMidwestern UniversityDowners GroveUSA

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