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Biologic Therapy of Leukemia pp 59–77Cite as

Radiolabeled Monoclonal Antibodies

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

Abstract

By targeting therapy to specific cell types and disease sites, monoclonal antibodies (MAbs) offer the possibility of improved efficacy and decreased toxicity compared with conventional chemotherapy. Nonetheless, the optimistic view of the early 1980s that MAbs were “magic bullets” has now been replaced by a more realistic understanding of their therapeutic potential. Since the 1980s various strategies employing MAbs for the treatment of cancer have evolved. Native MAbs can be used to focus an inflammatory response against a tumor cell. The binding of a MAb to a target cell can result in complement activation, thereby initiating several biologically important effects, including the induction of chemotaxis for phagocytic cells and the production of the membrane attack complex that disrupts cell membrane integrity. Anther important mechanism for tumor cell killing is antibody-dependent cell-mediated cytotoxicity (ADCC), in which an effector cell expressing an Fc receptor binds to a cell-bound MAb and is triggered to kill the target cell. Examples of antibodies with intrinsic immunologically mediated antitumor activity include the chimeric anti-CD20 antibody rituximab (1) and the humanized anti-CD52 antibody CAMPATH-1H for chronic lymphocytic leukemia (CLL) (2).

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References

  1. 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 

  2. Osterborg A, Dyer MJ, Bunjes D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol 1997; 15: 1567–1574.

    PubMed  CAS  Google Scholar 

  3. 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: 3244–3254.

    PubMed  CAS  Google Scholar 

  4. Kreitman RJ, Wilson WH, Bergeron K, et al. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med 2001; 345: 241–247.

    Article  PubMed  CAS  Google Scholar 

  5. Kaminski MS, Zelenetz AD, Press OW, et al. Pivotal study of iodine I 131 toxitumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol 2001; 19: 3918–3928.

    PubMed  CAS  Google Scholar 

  6. Witzig TE, White CA, Wiseman GA, et al. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999; 17: 3793–3803.

    PubMed  CAS  Google Scholar 

  7. Macklis RM, Lin JY, Beresford B, Atcher RW, Hines JJ, Humm JL. Cellular kinetics, dosimetry, and radiobiology of alpha-particle radioimmunotherapy: induction of apoptosis. Radiat Res 1992; 130: 220–226.

    Article  PubMed  CAS  Google Scholar 

  8. McDevitt MR, Sgouros G, Finn RD, et al. Radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med 1998; 25: 1341–1351.

    Article  PubMed  CAS  Google Scholar 

  9. Scheinberg DA, Strand M. Kinetic and catabolic considerations of monoclonal antibody targeting in erythroleukemic mice. Cancer Res 1983; 43: 265–272.

    PubMed  CAS  Google Scholar 

  10. Ali SA, Warren SD, Richter KY, et al. Improving tumor retention of radioiodinated antibody: aryl carbohydrate adducts. Cancer Res 1990; 50 (suppl): 783s - 788s.

    Google Scholar 

  11. Deshpande SV, DeNardo SJ, Kukis DL, et al. Yttrium-90-labeled monoclonal antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent. JNucl Med 1990; 31: 473–479.

    CAS  Google Scholar 

  12. Kosmas C, Snook D, Gooden CS, et al. Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmunoconjugates for imaging and therapy. Cancer Res 1992; 52: 904–911.

    PubMed  CAS  Google Scholar 

  13. Camera L, Kinuya S, Garmestani K, et al. Evaluation of the serum stability and in vivo biodistribution of CHX-DTPA and other ligands for yttrium labeling of monoclonal antibodies. J Nucl Med 1994; 35: 882–889.

    PubMed  CAS  Google Scholar 

  14. Nikula TK, McDevitt MR, Finn RD, et al. Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry. J Nucl Med 1999; 40: 166–176.

    PubMed  CAS  Google Scholar 

  15. Seitz U, Neumaier B, Glatting G, Kotzerke J, Bunjes D, Reske SN. Preparation and evaluation of the rhenium-188-labelled anti-NCA antigen monoclonal antibody BW 250/183 for radioimmunotherapy of leukaemia. Eur J Nucl Med 1999; 26: 1265–1273.

    Article  PubMed  CAS  Google Scholar 

  16. Larson SM. A tentative biological model for the localization of radiolabelled antibody in tumor: the improtance of immunoreactivity. Nucl Med Biol 1986; 13: 393–399.

    CAS  Google Scholar 

  17. Nikula TK, Bocchia M, Curcio MJ, et al. Impact of the high tyrosine fraction in complementarity-determining regions: measured and predicted effects of radioiodination on IgG immunoreactivity. Molec Immunol 1995; 32: 865–872.

    Article  CAS  Google Scholar 

  18. Scheinberg DA, Lovett D, Divgi DR, 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 

  19. Society of Nuclear Medicine. MIRD Primer for Absorbed Dose Calculations. Washington, DC: Society of Nuclear Medicine; 1988.

    Google Scholar 

  20. Koral KF, Zasadny KR, Kessler ML, et al. CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody of lymphoma. J Nucl Med 1994; 35: 1714–1720.

    PubMed  CAS  Google Scholar 

  21. Sgouros G, Chiu S, Pentlow KS, et al. Three-dimensional dosimetry for radioimmunotherapy treatment planning. J Nucl Med 1993; 34: 1595–1601.

    PubMed  CAS  Google Scholar 

  22. Sgouros G, Graham MC, Divgi CR, Larson SM, Scheinberg DA. Modeling and dosimetry of monoclonal antibody M195 (anti-CD33) in acute myelogenous leukemia. J Nucl Med 1993; 34: 422–430.

    PubMed  CAS  Google Scholar 

  23. Scheinberg DA, Tanimoto M, McKenzie S, Strife A, Old LJ, Clarkson BD. Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. Leukemia 1989; 3: 440 445.

    Google Scholar 

  24. Tanimoto M, Scheinberg DA, Cordon-Cardo C, Huie D, Clarkson BD, Old-LJ. Restricted expression of an early myeloid and monocytic cell surface antigen defined by monoclonal antibody M195. Leukemia 1989; 3: 339–348.

    PubMed  CAS  Google Scholar 

  25. Andrews RG, Torok-Storb B, Bernstein ID. Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies. Blood 1983; 62: 124–132.

    PubMed  CAS  Google Scholar 

  26. Griffin JD, Linch D, Sabbath K, Larcom P, Schlossman SE A monoclonal antibody reactive with normal and leukemic human myeloid progenitor cells. Leuk Res 1984; 8: 521–534.

    Article  PubMed  CAS  Google Scholar 

  27. Schwartz MA, Lovett DR, Redner A, et al. Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol 1993; 11: 294–303.

    PubMed  CAS  Google Scholar 

  28. Jurcic JG, Caron PC, Nikula TK, et al. Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. Cancer Res 1995; 55: 5908s - 5910s.

    PubMed  CAS  Google Scholar 

  29. Co MS, Avdalovic NM, Caron PC, Avdalovic MV, Scheinberg DA, Queen C. Chimeric and humanized antibodies with specificity for the CD33 antigen. J Immunol 1992; 148: 1149–1154.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  31. 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 

  32. Jurcic JG, DeBlasio T, Dumont L, Yao TJ, Scheinberg DA. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM 195 in acute promyelocytic leukemia. Clin Cancer Res 2000; 6: 372–380.

    PubMed  CAS  Google Scholar 

  33. 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 

  34. Jurcic JG, Caron PC, Miller WH Jr, et al. Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195. Leukemia 1995; 9: 244–248.

    PubMed  CAS  Google Scholar 

  35. Jurcic JG, Divgi CR, McDevitt MR, et al. Potential for myeloablation with yttrium-90HuM195 (anti-CD33) in myeloid leukemia [Abstract]. Proc Am Soc Clin Oncol 2000; 19: 8a.

    Google Scholar 

  36. Appelbaum FR, Matthews DC, Eary JF, et al. The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Transplantation 1992; 54: 829–833.

    Article  PubMed  CAS  Google Scholar 

  37. Ruffner KL, Matthews DC. Current uses of monoclonal antibodies in the treatment of acute leukemia. Semin Oncol 2000; 27: 531–539.

    PubMed  CAS  Google Scholar 

  38. Matthews DC, Appelbaum FR, Eary JF, et al. Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque. Blood 1991; 78: 1864–1874.

    PubMed  CAS  Google Scholar 

  39. Matthews DC, Appelbaum FR, Eary JF, et al. Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled antiCD45 antibody combined with cyclophosphamide and total body irradiation. Blood 1995; 85: 1122–1131.

    PubMed  CAS  Google Scholar 

  40. Matthews DC, Appelbaum FR, Eary JF, et al. Phase I study of (131)I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood 1999; 94: 1237–1247.

    PubMed  CAS  Google Scholar 

  41. Matthews DC, Appelbaum FR, Eary JF, Mitchell D, Press OW, Bernstein ID. 131I-antiCD45 antibody plus busulfan/cyclophosphamide in matched related transplants for AML in first remission [abstract]. Blood 1996; 88: 142a.

    Google Scholar 

  42. Bunjes D, Buchmann I, Duncker C, et al. Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study. Blood 2001; 98: 565–572.

    Article  PubMed  CAS  Google Scholar 

  43. Kotzerke J, Glatting G, Seitz U, et al. Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Reand 99mTc-labeled anti-NCA-95 MAbs. J Nucl Med 2000; 41: 531–537.

    PubMed  CAS  Google Scholar 

  44. Hueneke RB, Pippin CG, Sguire RA, Brechbiel MW, Gansow OA, Strand M. Effective alphaparticle-mediated radioimmunotherapy of murine leukemia. Cancer Res 1992; 52: 6095–6100.

    Google Scholar 

  45. Hartmann F, Horak EM, Garmestani K, et al. Radioimmunotherapy of nude mice bearing a human interleukin 2 receptor a-expressing lymphoma utilizing the a-emitting radionuclide-conjugated monoclonal antibody 212Bi-anti-Tac. Cancer Res 1994; 54: 4362–4370.

    PubMed  CAS  Google Scholar 

  46. McDevitt MR, Finn RD, Ma D, Larson SM, Scheinberg DA. Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use. J Nucl Med 1999; 40: 1722–1727.

    PubMed  CAS  Google Scholar 

  47. Jurcic JG, Larson SM, Sqouros G, et al. Targeted a particle immunotherapy for myeloid leukemia. Blood 2002; 100: 1233–1239.

    PubMed  CAS  Google Scholar 

  48. Sgouros G, Ballangrud AM, Jurcic JG, et al. Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. J Nucl Med 1999; 40: 1935–1946.

    PubMed  CAS  Google Scholar 

  49. McDevitt MR, Ma D, Lai LT, et al. Tumor therapy with targeted atomic nanogenerators. Science 2001; 294: 1537–1540.

    Article  PubMed  CAS  Google Scholar 

  50. Waldmann TA, White JD, Carrasquillo JA, et al. Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac. Blood 1995; 86: 4063–4075.

    PubMed  CAS  Google Scholar 

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Authors
  1. John M. Burke MD
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  2. Joseph G. Jurcic MD
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Editor information

Editors and Affiliations

  1. Leukemia Program, Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Matt Kalaycio MD

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© 2003 Humana Press Inc., Totowa, NJ

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Burke, J.M., Jurcic, J.G. (2003). Radiolabeled 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_5

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  • DOI: https://doi.org/10.1007/978-1-59259-383-5_5

  • 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

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