Skip to main content

Unconjugated Monoclonal Antibodies

  • Chapter
Biologic Therapy of Leukemia

Part of the book series: Contemporary Hematology ((CH))

  • 81 Accesses

Abstract

Monoclonal antibodies (MAbs) have been studied as a treatment for leukemia for approximately 20 years but have only recently been used successfully. The history of MAb development has been reviewed extensively (1–4). The purpose of this chapter is to review the clinical data supporting the use of unconjugated MAbs in the treatment of leukemia.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Levy R. A perspective on monoclonal antibody therapy: where we have been and where we are going. Sem Hematol 2000; 37: 43–46.

    Article  CAS  Google Scholar 

  2. Maloney DG. Advances in immunotherapy of hematologic malignancies. Curr Opin Hematol 1998; 5: 237–243.

    Article  PubMed  CAS  Google Scholar 

  3. Foon KA, Schroff RW, Bunn PA, Jr. Clinical applications of monoclonal antibodies for patients with leukemia and lymphoma. Prog Clin Biol Res 1986; 211: 265–284.

    PubMed  CAS  Google Scholar 

  4. Hainsworth JD. Monoclonal antibody therapy in lymphoid malignancies. Oncologist 2000; 5: 376–384.

    Article  PubMed  CAS  Google Scholar 

  5. Legrand O, Perrot JY, Baudard M, et al. The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score. Blood 2000; 96: 870–877.

    PubMed  CAS  Google Scholar 

  6. McGraw KJ, Rosenblum MG, Cheung L, Scheinberg DA. Characterization of murine and humanized anti-CD33, gelonin immunotoxins reactive against myeloid leukemias. Cancer Immunol Immunother 1994; 39: 367–374.

    Article  PubMed  CAS  Google Scholar 

  7. Scheinberg DA, Lovett D, Divgi CR, et al. A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide. J Clin Oncol 1991; 9: 478–490.

    PubMed  CAS  Google Scholar 

  8. Caron PC, Co MS, Bull MK, Avdalovic NM, Quenn C, Scheinberg DA. Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res 1992; 52: 6761–6767.

    PubMed  CAS  Google Scholar 

  9. Caron PC, Jurcic JG, Scott AM, et al. A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity. Blood 1994; 83: 1760–1768.

    PubMed  CAS  Google Scholar 

  10. Caron PC, Dumont L, Scheinberg DA. Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia. Clin Cancer Res 1998; 4: 1421–1428.

    PubMed  CAS  Google Scholar 

  11. Jurcic JG, DeBlasio T, Dumont L, Yao TJ, Scheinberg DA. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res 2000; 6: 372–380.

    PubMed  CAS  Google Scholar 

  12. Feldman E, Kalaycio M, Schulman P, et al. Humanized monoclonal anti-CD33 antibody HuM195 in the treatment of relapsed/refractory acute myelogenous leukemia (AML): preliminary report of a phase II trial. Proc Am Soc Clin Oncol 1999; 18: 4a.

    Google Scholar 

  13. Feldman E, Stone RM, Brandwein J, et al. Phase III randomized trial of an anti-CD33 monoclonal antibody (HUM195) in combination with chemotherapy compared to chemotherapy alone in adults with refractory of first-relapse acute myeloid leukemia. Proc Am Soc Clin Oncol 2002; 21: 261a.

    Google Scholar 

  14. Hofmeister JK, Cooney D, Coggeshall KM. Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis. Blood Cells Molecules, Dis 2000; 26: 133–143.

    CAS  Google Scholar 

  15. Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 2000; 95: 3900–3908.

    PubMed  CAS  Google Scholar 

  16. Clynes RA, Towers TL, Presta LG, Ravetch N. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Med 2000; 6: 443–446.

    Article  PubMed  CAS  Google Scholar 

  17. Shan D, Ledbetter JA, Press OW. Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells. Cancer Immunol Immunother 2000; 48: 673–683.

    Article  PubMed  CAS  Google Scholar 

  18. McLaughlin P, Hagemeister FB, Grillo-Lopez AJ. Rituximab in indolent lymphoma: the single-agent pivotal trial. Sem Oncol 1999; 26: 79–87.

    CAS  Google Scholar 

  19. Caligaris-Cappio F. B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. Blood 1996; 87: 2615–2620.

    PubMed  CAS  Google Scholar 

  20. Ladetto M, Bergui L, Ricca I, Campana S, Pileri A, Tarella C. Rituximab anti-CD20 monoclonal antibody induces marked but transient reductions of peripheral blood lymphocytes in chronic lymphocytic leukaemia patients. Med Oncol 2000; 17: 203–210.

    Article  PubMed  CAS  Google Scholar 

  21. Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999; 94: 2217–2224.

    PubMed  CAS  Google Scholar 

  22. Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood 2001; 98: 1326–1331.

    Article  PubMed  CAS  Google Scholar 

  23. Dillman RO. Infusion reactions associated with the therapeutic use of monoclonal antibodies in the treatment of malignancy. Cancer Metastasis Rev 1999; 18: 465–471.

    Article  PubMed  CAS  Google Scholar 

  24. Dyer MJ. The role of CAMPATH-1 antibodies in the treatment of lymphoid malignancies. Sem Oncol 1999; 26: 52–57.

    CAS  Google Scholar 

  25. Kunkel L, Wong A, Maneatis T, et al. Optimizing the use of rituximab for treatment of B-cell non-Hodgkin’s lymphoma: a benefit-risk update. Sem Oncol 2000; 27: 53–61.

    CAS  Google Scholar 

  26. Yang H, Rosove MH, Figlin RA. Tumor lysis syndrome occurring after the administration of rituximab in lymphoproliferative disorders: high-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Am Hematol 1999; 62: 247–250.

    Article  CAS  Google Scholar 

  27. Byrd JC, Waselenko JK, Maneatis TJ, et al. Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance. J Clin Oncol 1999; 17: 791–795.

    PubMed  CAS  Google Scholar 

  28. O’Brien SM, Kantarjian H, Thomas DA, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol 2001; 19: 2165–2170.

    PubMed  Google Scholar 

  29. Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 2001; 19: 2153–2164.

    PubMed  CAS  Google Scholar 

  30. Garcia-Manero G, O’Brien S, Cortes J, et al. Combination fludarabine, cyclophosphamide, and rituximab for previously treated patients with chronic lymphocytic leukemia. Blood 2000; 96: 757a.

    Google Scholar 

  31. Wierda W, O’Brien S, Albitar M, et al. Combined fludarabine, cyclophosphamide, and rituximab achieves a high complete remission rate as initial treatment for chronic lymphocytic leukemia. Blood 2001; 98: 771a.

    Google Scholar 

  32. Flinn IW, Byrd JC, Morrison C, et al. Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood 2000; 96: 71–75.

    PubMed  CAS  Google Scholar 

  33. Golay J, Xiao YM, Di Gaetano N, Dastoli G, Rambaldi A, Introna M. Fludarabine synergises with anti CD20 monoclonal antibody rituximab in complement mediated cell lysis. Blood 2000; 96: 339a.

    Google Scholar 

  34. Hagberg H. Chimeric monoclonal anti-CD20 antibody (rituximab)-an effective treatment for a patient with relapsing hairy cell leukaemia. Med Oncol 1999; 16: 221–222.

    Article  PubMed  CAS  Google Scholar 

  35. Thomas DA, O’Brien S, Cortes J, et al. Pilot study of rituximab in refractory or relapsed hairy cell leukemia. Blood 1999; 94: 705a.

    Google Scholar 

  36. Nieva J, Bethel K, Baker T, Saven A. Phase II study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood 2001; 98: 364a - 365a.

    Google Scholar 

  37. Domagala A, Kurpisz M. CD52 antigen-a review. Med Sci Monitor 2001; 7: 325–331.

    CAS  Google Scholar 

  38. Hale G, Bright S, Chumbley G, et al. Removal of T-cells from bone marrow for transplantation: a monoclonal antibody fixes human complement. Blood 1983; 62: 873–882.

    PubMed  CAS  Google Scholar 

  39. Dyer MJS, Hale G, Hayhoe FHJ, Waldmann H Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies. Blood 1989; 73: 1431–1439.

    PubMed  CAS  Google Scholar 

  40. Hale G, Dyer MJ, Clark MR, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet 1988; 2: 1394–1399.

    Article  PubMed  CAS  Google Scholar 

  41. Hale G, Zhang MJ, Bunjes D, et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Blood 1998; 92: 4581–4590.

    PubMed  CAS  Google Scholar 

  42. Kottaridis PD, Milligan DW, Chopra R, et al. In vivo CAMPATH-1H prevents graft-versushost disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    PubMed  CAS  Google Scholar 

  43. Cull GM, Haynes AP, Byrne JL, et al. Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH conditioning: an effective regimen with low procedure-related toxicity. Br J Haematol 2000; 108: 754–760.

    Article  PubMed  CAS  Google Scholar 

  44. Pangalis GA, Dimopoulou MN, Angelopoulou MK, Tsekouras CH, Siakantaris MP. Campath-1H in B-chronic lymphocytic leukemia: report on a patient treated thrice in a 3 year period. Med Oncol 2000; 17: 70–73.

    Article  PubMed  CAS  Google Scholar 

  45. Lundin J, Osterborg A, Brittinger G, et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin’s Lymphoma. J Clin Oncol 1998; 16: 3257–3263.

    PubMed  CAS  Google Scholar 

  46. Dyer MJS, Osterborg A. The use of therapeutic monoclonal antibodies in chronic lymphocytic leukemia. In: Cheson BD, ed. Chronic Lymphoid Leukemias. New York: Marcel Dekker; 2001: 335–352.

    Google Scholar 

  47. Pawson R, Dyer MJS, Barge R, et al. Treatment of T-cell prolymphocytic leukemia with human anti-CD52 antibody. J Clin Oncol 1997; 15: 2667–2672.

    PubMed  CAS  Google Scholar 

  48. Dearden CE, Matutes E, Cazin B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood 2001; 98: 1721–1726.

    Article  PubMed  CAS  Google Scholar 

  49. Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J Clin Oncol 1994; 12: 2588–2593.

    PubMed  CAS  Google Scholar 

  50. Osterborg A, Dyer MJS, Bunjes D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. J Clin Oncol 1997; 15: 1567–1574.

    PubMed  CAS  Google Scholar 

  51. Bowen AL, Zomas A, Emmett E, Matutes E, Dyer MDC. Subcutaneous CAMPATH-1H in fludarabine-resistant/relapsed chronic lymphocytic and B-prolymphocytic leukaemia. Br J Haematol 1997; 96: 617–619.

    Article  PubMed  CAS  Google Scholar 

  52. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (CAMPATH-1H) in patients who have failed fludarabine: results of a large international study. Blood 2002; 99: 3554–3561.

    Article  PubMed  CAS  Google Scholar 

  53. Osterborg A, Fassa AS, Anagnostopoulos A, Dyer MJS, Catovsky D, Mellstedt H. Humanized CD52 monoclonal antibody CAMPATH-1H as first-line treatment in chronic lymphocytic leukemia. Br J Haematol 1996; 93: 151–153.

    Article  PubMed  CAS  Google Scholar 

  54. O’Brien SM, Thomas DA, Cortes J, et al. CAMPATH-1H for minimal residual disease in chronic lymphocytic leukemia. J Clin Oncol 2001; 21: 284a.

    Google Scholar 

  55. Lundin J, Kimby E, Bjorkholm M, et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzuzmab (Campath-1H) as first line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100: 768–773.

    Article  PubMed  CAS  Google Scholar 

  56. Kostelny SA, Link BK, Tso JY, et al. Humanization and characterization of the anti-HLADR antibody 1D10. Int J Cancer 2001; 93: 556–565.

    Article  PubMed  CAS  Google Scholar 

  57. Foon KA, Schroff RW, Bunn PA, et al. Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia. Blood 1984; 64: 1085–1093.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Kalaycio, M. (2003). Unconjugated Monoclonal Antibodies. In: Kalaycio, M. (eds) Biologic Therapy of Leukemia. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-383-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-383-5_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9777-9

  • Online ISBN: 978-1-59259-383-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics