Skip to main content
SpringerLink
Log in
Book cover

Immunotherapy for Pediatric Malignancies pp 65–78Cite as

Overview of Monoclonal Antibody Therapies

  • Chapter
  • First Online:

Abstract

The advent of monoclonal antibody technology in the 1970s brought with it the possibility of generating virtually unlimited amounts of pure antibody targeting almost any antigen of choice, opening the door to widespread application. Since the first monoclonal antibody was licensed for clinical use 30 years ago, there has been an exponential growth in our knowledge of how they may be used therapeutically, particularly in the treatment to cancer. The attraction of antibodies as therapeutics lies in part in their exquisite specificity, with little off target binding, but also in their relative ease of production and storage (as compared to cellular immunotherapies) and their long in vivo half-life (as compared to small molecules). Although the development of monoclonal antibodies for paediatric cancers has lagged behind their use for adult malignancies, there are increasing numbers of antibodies in paediatric clinical trials, and in 2015, dinutuximab, the first monoclonal antibody specifically for a paediatric malignancy (neuroblastoma), was approved.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Winau F, Winau R. Emil von Behring and serum therapy. Microbes Infect. 2002;4(2):185–8.

    Article  PubMed  Google Scholar 

  2. Strebhardt K, Ullrich A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer. 2008;8(6):473–80.

    Article  CAS  PubMed  Google Scholar 

  3. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256(5517):495–7.

    Article  CAS  PubMed  Google Scholar 

  4. Liu JK. The history of monoclonal antibody development—progress, remaining challenges and future innovations. Ann Med Surg (Lond). 2014;3(4):113–6.

    Article  Google Scholar 

  5. Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR. Making antibodies by phage display technology. Annu Rev Immunol. 1994;12:433–55.

    Article  CAS  PubMed  Google Scholar 

  6. Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC Jr. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res. 1985;45(2):879–85.

    CAS  PubMed  Google Scholar 

  7. Shawler DL, Bartholomew RM, Smith LM, Dillman RO. Human immune response to multiple injections of murine monoclonal IgG. J Immunol. 1985;135(2):1530–5.

    CAS  PubMed  Google Scholar 

  8. Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312(5995):643–6.

    Article  CAS  PubMed  Google Scholar 

  9. Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984;81(21):6851–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Glennie MJ, Johnson PW. Clinical trials of antibody therapy. Immunol Today. 2000;21(8):403–10.

    Article  CAS  PubMed  Google Scholar 

  11. Pavlinkova G, Colcher D, Booth BJ, Goel A, Wittel UA, Batra SK. Effects of humanization and gene shuffling on immunogenicity and antigen binding of anti-TAG-72 single-chain Fvs. Int J Cancer. 2001;94(5):717–26.

    Article  CAS  PubMed  Google Scholar 

  12. Clark M. Antibody humanization: a case of the ‘Emperor’s new clothes’? Immunol Today. 2000;21(8):397–402.

    Article  CAS  PubMed  Google Scholar 

  13. Bruggemann M, Spicer C, Buluwela L, Rosewell I, Barton S, Surani MA, et al. Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus. Eur J Immunol. 1991;21(5):1323–6.

    Article  CAS  PubMed  Google Scholar 

  14. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140–74.

    Article  CAS  PubMed  Google Scholar 

  15. Siebert N, Eger C, Seidel D, Juttner M, Zumpe M, Wegner D, et al. Pharmacokinetics and pharmacodynamics of ch14.18/CHO in relapsed/refractory high-risk neuroblastoma patients treated by long-term infusion in combination with IL-2. MAbs. 2016;8(3):604–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Albertini MR, Gan J, Jaeger P, Hank JA, Storer B, Schell K, et al. Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2 antibody in patients with melanoma. J Immunother Emphasis Tumor Immunol. 1996;19(4):278–95.

    Article  CAS  PubMed  Google Scholar 

  17. Albertini MR, Hank JA, Schiller JH, Khorsand M, Borchert AA, Gan J, et al. Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients. Clin Cancer Res. 1997;3(8):1277–88.

    CAS  PubMed  Google Scholar 

  18. Davis TA, Maloney DG, Czerwinski DK, Liles TM, Levy R. Anti-idiotype antibodies can induce long-term complete remissions in non-Hodgkin’s lymphoma without eradicating the malignant clone. Blood. 1998;92(4):1184–90.

    CAS  PubMed  Google Scholar 

  19. Pesando JM, Hoffman P, Abed M. Antibody-induced antigenic modulation is antigen dependent: characterization of 22 proteins on a malignant human B cell line. J Immunol. 1986;137(11):3689–95.

    CAS  PubMed  Google Scholar 

  20. Glennie MJ, van de Winkel JG. Renaissance of cancer therapeutic antibodies. Drug Discov Today. 2003;8(11):503–10.

    Article  CAS  PubMed  Google Scholar 

  21. Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol. 2008;8(1):34–47.

    Article  CAS  PubMed  Google Scholar 

  22. Seidel UJ, Schlegel P, Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Front Immunol. 2013;4:76.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rafiq K, Bergtold A, Clynes R. Immune complex-mediated antigen presentation induces tumor immunity. J Clin Invest. 2002;110(1):71–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670–90.

    Article  CAS  Google Scholar 

  25. Rogers LM, Veeramani S, Weiner GJ. Complement in monoclonal antibody therapy of cancer. Immunol Res. 2014;59(1–3):203–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sorkin LS, Otto M, Baldwin WM 3rd, Vail E, Gillies SD, Handgretinger R, et al. Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia. Pain. 2010;149(1):135–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012;12(4):278–87.

    Article  CAS  PubMed  Google Scholar 

  28. Lim SH, Beers SA, French RR, Johnson PW, Glennie MJ, Cragg MS. Anti-CD20 monoclonal antibodies: historical and future perspectives. Haematologica. 2010;95(1):135–43.

    Article  CAS  PubMed  Google Scholar 

  29. Alvarez-Rueda N, Desselle A, Cochonneau D, Chaumette T, Clemenceau B, Leprieur S, et al. A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity. PLoS One. 2011;6(9):e25220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cheung NK, Sowers R, Vickers AJ, Cheung IY, Kushner BH, Gorlick R. FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. J Clin Oncol. 2006;24(18):2885–90.

    Article  CAS  PubMed  Google Scholar 

  31. Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008;26(11):1789–96.

    Article  CAS  PubMed  Google Scholar 

  32. Weng WK, Levy R. Genetic polymorphism of the inhibitory IgG Fc receptor FcgammaRIIb is not associated with clinical outcome in patients with follicular lymphoma treated with rituximab. Leuk Lymphoma. 2009;50(5):723–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Homet Moreno B, Ribas A. Anti-programmed cell death protein-1/ligand-1 therapy in different cancers. Br J Cancer. 2015;112(9):1421–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee CS, Cragg M, Glennie M, Johnson P. Novel antibodies targeting immune regulatory checkpoints for cancer therapy. Br J Clin Pharmacol. 2013;76(2):233–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Marabelle A, Gray J. Tumor-targeted and immune-targeted monoclonal antibodies: going from passive to active immunotherapy. Pediatr Blood Cancer. 2015;62(8):1317–25.

    Article  CAS  PubMed  Google Scholar 

  37. Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15(6):385–403.

    Article  CAS  PubMed  Google Scholar 

  38. Sullivan LA, Brekken RA. The VEGF family in cancer and antibody-based strategies for their inhibition. MAbs. 2010;2(2):165–75.

    Article  PubMed  PubMed Central  Google Scholar 

  39. de Goeij BE, Lambert JM. New developments for antibody-drug conjugate-based therapeutic approaches. Curr Opin Immunol. 2016;40:14–23.

    Article  PubMed  Google Scholar 

  40. Isaacs JD, Greenwood J, Waldmann H. Therapy with monoclonal antibodies. II. The contribution of Fc gamma receptor binding and the influence of C(H)1 and C(H)3 domains on in vivo effector function. J Immunol. 1998;161(8):3862–9.

    CAS  PubMed  Google Scholar 

  41. Herter S, Birk MC, Klein C, Gerdes C, Umana P, Bacac M. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity. J Immunol. 2014;192(5):2252–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Navid F, Sondel PM, Barfield R, Shulkin BL, Kaufman RA, Allay JA, et al. Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J Clin Oncol. 2014;32(14):1445–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. DiLillo DJ, Ravetch JV. Fc-receptor interactions regulate both cytotoxic and immunomodulatory therapeutic antibody effector functions. Cancer Immunol Res. 2015;3(7):704–13.

    Article  CAS  PubMed  Google Scholar 

  44. Beers SA, Glennie MJ, White AL. Influence of immunoglobulin isotype on therapeutic antibody function. Blood. 2016;127(9):1097–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. White AL, Dou L, Chan HT, Field VL, Mockridge CI, Moss K, et al. Fcgamma receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization. J Immunol. 2014;193(4):1828–35.

    Article  CAS  PubMed  Google Scholar 

  46. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363(14):1324–34.

    Google Scholar 

  47. Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COGANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017;18(7):946–957. doi: 10.1016/S1470-2045(17)30355-8. Epub 2017 May 23.

    Google Scholar 

  48. Morris ZS, Guy EI, Francis DM, Gressett MM, Werner LR, Carmichael LL, et al. In situ tumor vaccination by combining local radiation and tumor-specific antibody or immunocytokine treatments. Cancer Res. 2016;76(13):3929–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Sciences Unit, University of Southampton, Southampton, UK

    Juliet C. Gray M.A., FRCPCH, Ph.D.

  2. Departments of Pediatrics, Human Oncology, and Genetics, University of Wisconsin, American Family Children’s Hospital, Madison, WI, USA

    Paul M. Sondel M.D., Ph.D.

Authors
  1. Juliet C. Gray M.A., FRCPCH, Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul M. Sondel M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juliet C. Gray M.A., FRCPCH, Ph.D. .

Editor information

Editors and Affiliations

  1. Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom

    Juliet C. Gray

  2. Département d’Innovation Thérapeutique et d'Essais Précoces, University of Paris-Saclay Gustave Roussy, Villejuif, France

    Aurélien Marabelle

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Gray, J.C., Sondel, P.M. (2018). Overview of Monoclonal Antibody Therapies. In: Gray, J., Marabelle, A. (eds) Immunotherapy for Pediatric Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-43486-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-43486-5_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-43484-1

  • Online ISBN: 978-3-319-43486-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation