Gemtuzumab ozogamicin and Antibody Engineering

Gemtuzumab ozogamicin과 항체공학

  • Received : 2009.10.15
  • Accepted : 2009.11.22
  • Published : 2009.12.31

Abstract

Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.

Keywords

References

  1. Burnett AK. Transplantation in first remission of acute myeloid leukemia. New England Journal of Medicine 1998; 339: 1698-700. https://doi.org/10.1056/NEJM199812033392309
  2. Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology (American Society of Hematology Education Program) 2004; 98-117.
  3. Bross PF, Beitz J, Chen G et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clinical Cancer Research 2001; 7: 1490-96.
  4. Freeman SD, Kelm S, Barber EK et al. Characterization of CD33 as a new member of the sialo adhesin family of cellular interaction molecules. Blood 1995; 85: 2005-12.
  5. Tchilian EZ, Beverley PC, Young BD et al. Molecular cloning of two isoforms of the murine homolog of the myeloid CD33 antigen. Blood 1994; 83: 3188-98.
  6. Gao Z, McAlister VC, Williams GM Repopulation of liver endothelium by bone-marrow-derived cells. Lancet 2001; 357: 932-3. https://doi.org/10.1016/S0140-6736(00)04217-3
  7. Zein N, Sinha AM, McGahren WJ et al. Calicheamicin gamma 1I: an antitumor antibiotic that cleaves doublestranded DNA site specifically. Science 1988; 240: 1198-201. https://doi.org/10.1126/science.3240341
  8. Sievers EL, Appelbaum FR, Spielberger RT et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calichea micin immunoconjugate. Blood 1999; 93(11): 3678-84.
  9. Hamann PR, Hinman LM, Hollander I et al. Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibodycalicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjugate Chem 2002; 13: 47-58. https://doi.org/10.1021/bc010021y
  10. Hamann PR, Hinman LM, Beyer CF, et al. An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjugate Chem 2002; 13: 40-6. https://doi.org/10.1021/bc0100206
  11. Lee MD, Ellestad GA, Borders DB. Calicheamicins: discovery, structure, chemistry, and interaction with DNA. Acc Chem Res 1991; 24: 235-43. https://doi.org/10.1021/ar00008a003
  12. Korth-Bradley JM, Dowell JA, King SP et al. Impact of age and gender on the pharmacokinetics of gemtuzumab ozogamicin. Pharmacotherapy 2001; 21: 1175-80. https://doi.org/10.1592/phco.21.15.1175.33890
  13. Wyeth Laboratories. Mylotarg(gemtuzumab ozogamicin for injection)[online]. Available from URL: http:// www.wyeth. com.
  14. product Information. Mylotarg(TM), gemtuzumab ozogamicin. Wyeth Laboratories, Philadelphia, PA, 2001.
  15. Leopold LH, Berger MS, Feingold J. Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg) therapy of acute myeloid leukemia. Clin Lymphoma 2002; (2 Suppl 1): S29-S34.
  16. Sievers EL, Larson RA, Stadtmauer EA et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33- positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19: 3244-54. https://doi.org/10.1200/JCO.2001.19.13.3244
  17. Tang W, Ziring D, Gershman G, French S. Role of macrophages and stellate cells in the pathogenesis of venoocclusive disease: an electron microscopic case study. Exp Mol Pathol 2003; 75(3): 201-9. https://doi.org/10.1016/S0014-4800(03)00094-7
  18. Aalberse RC, Stapel SO, Schuurmanw J et al. Immuno globulin G4: an odd antibody, Clinical & Experimental Allergy 2009; 39: 469-77. https://doi.org/10.1111/j.1365-2222.2009.03207.x
  19. Aran FL, Antonio OB, Ewald TJ et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. nature biotechnology 2009; 27(8): 767-71. https://doi.org/10.1038/nbt.1553
  20. Bross PF, Beitz J, Chen G et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res 2001; 7(6): 1490-6.
  21. Anna MW, Peter DS. Arming antibodies: prospects and challenges for immunoconjugates, Nature biotechnology 2005; 23(9): 1137-46. https://doi.org/10.1038/nbt1141
  22. Stasi R. Gemtuzumab ozogamicin : an anti-CD33 immun oconjugate for the treatment of acute myeloid leukaemia. Expert Opin. Biol Ther. 2008; 8(4): 527-40. https://doi.org/10.1517/14712598.8.4.527
  23. Stern M, Herrmann R. Overview of monoclonal antibodies in cancer therapy: present and promise. Crit Rev Oncol Hematol 2005; 54(1): 11-29. https://doi.org/10.1016/j.critrevonc.2004.10.011