Skip to main content
SpringerLink
Log in

Antibody-Based Therapeutics Targeting CD33, CD45, and CD66

  • Chapter
  • First Online:
Targeted Therapy of Acute Myeloid Leukemia

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Targeted therapy of acute myeloid leukemia (AML) with monoclonal antibodies (MoAbs) has thus far been mostly directed at CD33, CD45, and CD66. The notion that some AMLs may predominantly or entirely involve committed CD33+ myeloid precursors provided the rationale for eradicating underlying stem cells with anti-CD33 antibodies. Emerging data demonstrating efficacy of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, in acute promyelocytic leukemia and other favorable- and intermediate-risk AMLs validate CD33 as drug target. Unlike CD33, CD45 and CD66 are noninternalizing antigens and have primarily been targeted to deliver radionuclides to sites of hematopoietic tissue, particularly to augment pre-transplant conditioning regimens. Early studies document the feasibility of this approach in selected patients, although future controlled studies will need to assess whether this strategy indeed leads to improved outcomes. Given this encouraging clinical experience, the use of MoAbs is likely expanding significantly in the future with identification of additional AML (stem) cell-associated antigens.

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

Access this chapter

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

References

  • Abutalib SA, Tallman MS (2006) Monoclonal antibodies for the treatment of acute myeloid leukemia. Curr Pharm Biotechnol 7:343–369

    Article  CAS  PubMed  Google Scholar 

  • Andres TL, Kadin ME (1983) Immunologic markers in the differential diagnosis of small round cell tumors from lymphocytic lymphoma and leukemia. Am J Clin Pathol 79:546–552

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Andrews RG, Takahashi M, Segal GM et al (1986) The L4F3 antigen is expressed by unipotent and multipotent colony-forming cells but not by their precursors. Blood 68:1030–1035

    CAS  PubMed  Google Scholar 

  • Appelbaum FR (1999) Antibody-targeted therapy for myeloid leukemia. Semin Hematol 36:2–8

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Becker W, Goldenberg DM, Wolf F (1994) The use of monoclonal antibodies and antibody fragments in the imaging of infectious lesions. Semin Nucl Med 24:142–153

    Article  CAS  PubMed  Google Scholar 

  • Bernstein ID, Singer JW, Andrews RG et al (1987) Treatment of acute myeloid leukemia cells in vitro with a monoclonal antibody recognizing a myeloid differentiation antigen allows normal progenitor cells to be expressed. J Clin Invest 79:1153–1159

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bernstein ID, Singer JW, Smith FO et al (1992) Differences in the frequency of normal and clonal precursors of colony-forming cells in chronic myelogenous leukemia and acute myelogenous leukemia. Blood 79:1811–1816

    CAS  PubMed  Google Scholar 

  • Breccia M, Lo-Coco F (2011) Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia: mechanisms of action and resistance, safety and efficacy. Expert Opin Biol Ther 11:225–234

    Article  CAS  PubMed  Google Scholar 

  • Breccia M, Cimino G, Diverio D et al (2007) Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia. Haematologica 92:1273–1274

    Article  CAS  PubMed  Google Scholar 

  • Bross PF, Beitz J, Chen G et al (2001) Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res 7:1490–1496

    CAS  PubMed  Google Scholar 

  • Bunjes D (2002) 188Re-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia. Leuk Lymphoma 43:2125–2131

    Article  CAS  PubMed  Google Scholar 

  • Bunjes D, Buchmann I, Duncker C et al (2001) 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 98:565–572

    Article  CAS  PubMed  Google Scholar 

  • Burnett AK, Hills RK, Milligan D et al (2011) Identification of patients with acute myeloblastic leukaemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial J Clin Oncol 29:369–377

    Article  CAS  PubMed  Google Scholar 

  • Burnett AK, Russell N, Hill RK et al (2012) The addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 30(32):3924–3931

    Google Scholar 

  • Caron PC, Co MS, Bull MK et al (1992) Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res 52:6761–6767

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Castaigne S, Pautas C, Terré C et al (2012) Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 379:1508–1516

    Article  CAS  PubMed  Google Scholar 

  • Clift RA, Buckner CD, Appelbaum FR et al (1990) Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 76:1867–1871

    CAS  PubMed  Google Scholar 

  • Clift RA, Buckner CD, Appelbaum FR et al (1998) Long-term follow-up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood 92:1455–1456

    CAS  PubMed  Google Scholar 

  • Dahlke MH, Larsen SR, Rasko JE et al (2004) The biology of CD45 and its use as a therapeutic target. Leuk Lymphoma 45:229–236

    Google Scholar 

  • Delaunay J, Recher C, Pigneux A et al (2011) Addition of gemtuzumab ozogamycin to chemotherapy improves event-free survival but not overall survival of AML patients with intermediate cytogenetics not eligible for allogeneic transplantation. Results of the GOELAMS AML 2006 IR study [abstract #79]. Blood 118:37–38

    Article  Google Scholar 

  • Dick JE (2008) Stem cell concepts renew cancer research. Blood 112:4793–4807

    Article  CAS  PubMed  Google Scholar 

  • Dinndorf PA, Andrews RG, Benjamin D et al (1986) Expression of normal myeloid-associated antigens by acute leukemia cells. Blood 67:1048–1053

    CAS  PubMed  Google Scholar 

  • Estey EH, Giles FJ, Beran M et al (2002) Experience with gemtuzumab ozogamycin (“mylotarg”) and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood 99:4222–4224

    Article  CAS  PubMed  Google Scholar 

  • Farhat H, Reman O, Raffoux E et al (2012) Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70-year old: a phase 1/2 study of the acute leukemia French association. Am J Hematol 87:62–65

    Article  CAS  PubMed  Google Scholar 

  • Feldman E, Kalaycio M, Weiner G et al (2003) Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. Leukemia 17:314–318

    Article  CAS  PubMed  Google Scholar 

  • Feldman EJ, Brandwein J, Stone R et al (2005) Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol 23:4110–4116

    Article  CAS  PubMed  Google Scholar 

  • Fenton C, Perry CM (2005) Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia. Drugs 65:2405–2427

    Article  CAS  PubMed  Google Scholar 

  • Fialkow PJ, Singer JW, Adamson JW et al (1981) Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. Blood 57:1068–1073

    CAS  PubMed  Google Scholar 

  • Fialkow PJ, Singer JW, Raskind WH et al (1987) Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. N Engl J Med 317:468–473

    Article  CAS  PubMed  Google Scholar 

  • Giles F, Estey E, O’brien S (2003) Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer 98:2095–2104

    Article  CAS  PubMed  Google Scholar 

  • Goemans BF, Zwaan CM, Vijverberg SJ et al (2008) Large interindividual differences in cellular sensitivity to calicheamicin may influence gemtuzumab ozogamicin response in acute myeloid leukemia. Leukemia 22:2284–2285

    Article  CAS  PubMed  Google Scholar 

  • Gray-Owen SD, Blumberg RS (2006) CEACAM1: contact-dependent control of immunity. Nature Rev 6:433–446

    CAS  Google Scholar 

  • Green DJ, Pagel JM, Nemecek ER et al (2009) Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates. Blood 114:1226–1235

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Griffin JD, Linch D, Sabbath K et al (1984) A monoclonal antibody reactive with normal and leukemic human myeloid progenitor cells. Leuk Res 8:521–534

    Article  CAS  PubMed  Google Scholar 

  • Grimwade D, Enver T (2004) Acute promyelocytic leukemia: where does it stem from? Leukemia 18:375–384

    Article  CAS  PubMed  Google Scholar 

  • Jager E, Van Der Velden VHJ, Te Marvelde JG et al (2011) Targeted drug delivery by gemtuzumab ozogamicin: mechanism-based mathematical model for treatment strategy improvement and therapy individualization. PLoS One 6:e24265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jordan CT, Guzman ML (2004) Mechanisms controlling pathogenesis and survival of leukemic stem cells. Oncogene 23:7178–7187

    Article  CAS  PubMed  Google Scholar 

  • Jurcic JG (2001) Antibody therapy for residual disease in acute myelogenous leukemia. Crit Rev Oncol Hematol 38:37–45

    Article  CAS  PubMed  Google Scholar 

  • Jurcic JG, Deblasio T, Dumont L et al (2000) Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res 6:372–380

    CAS  PubMed  Google Scholar 

  • Jurcic JG, Larson SM, Sgouros G et al (2002) Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100:1233–1239

    CAS  PubMed  Google Scholar 

  • Kelly LM, Gilliland DG (2002) Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 3:179–198

    Article  CAS  PubMed  Google Scholar 

  • Klein SA, Hermann S, Dietrich JW et al (2002) Transplantation-related toxicity and acute intestinal graft-versus-host disease after conditioning regimens intensified with Rhenium 188-labeled anti-CD66 monoclonal antibodies. Blood 99:2270–2271

    Article  CAS  PubMed  Google Scholar 

  • Koenecke C, Hofmann M, Bolte O et al (2008) Radioimmunotherapy with [(188)Re]-labelled anti-CD66 antibody in the conditioning for allogeneic stem cell transplantation for high-risk acute myeloid leukemia. Int J Hematol 87:414–421

    Article  PubMed  Google Scholar 

  • Lane SW, Gilliland DG (2010) Leukemia stem cells. Semin Cancer Biol 20:71–76

    Article  CAS  PubMed  Google Scholar 

  • Lapusan S, Vidriales MB, Thomas X et al (2012) Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest New Drugs 30:1121–1131

    Article  CAS  PubMed  Google Scholar 

  • Larson RA, Sievers EL, Stadtmauer EA et al (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104:1442–1452

    Article  CAS  PubMed  Google Scholar 

  • Linenberger ML (2005) CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia 19:176–182

    Article  CAS  PubMed  Google Scholar 

  • Lo-Coco F, Cimino G, Breccia M et al (2004) Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood 104:1995–1999

    Article  CAS  PubMed  Google Scholar 

  • Majeti R (2011) Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene 30:1009–1019

    Article  CAS  PubMed  Google Scholar 

  • Matthews DC, Appelbaum FR (2004) Radioimmunotherapy and hematopoietic cell transplantation. In: Blume KG, Forman SJ, Appelbaum FR (eds) Thomas’ hematopoietic cell transplantion, 3rd edn. Blackwell Publishing Ltd, Massachusetts, pp 198–208

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Matthews DC, Badger CC, Fisher DR et al (1992) Selective radiation of hematolymphoid tissue delivered by anti-CD45 antibody. Cancer Res 52:1228–1234

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Mcdevitt MR, Finn RD, Ma D et al (1999) Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use. J Nucl Med 40:1722–1727

    CAS  PubMed  Google Scholar 

  • Mcdevitt MR, Ma D, Lai LT et al (2001) Tumor therapy with targeted atomic nanogenerators. Science 294:1537–1540 (New York)

    Article  CAS  PubMed  Google Scholar 

  • Miederer M, Mcdevitt MR, Sgouros G et al (2004) Pharmacokinetics, dosimetry, and toxicity of the targetable atomic generator, 225Ac-HuM195, in nonhuman primates. J Nucl Med 45:129–137

    CAS  PubMed  Google Scholar 

  • Nakano A, Harada T, Morikawa S et al (1990) Expression of leukocyte common antigen (CD45) on various human leukemia/lymphoma cell lines. Acta Pathol Jpn 40:107–115

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Pagano L, Fianchi L, Caira M et al (2007) The role of gemtuzumab ozogamicin in the treatment of acute myeloid leukemia patients. Oncogene 26:3679–3690

    Article  CAS  PubMed  Google Scholar 

  • Pagel JM, Appelbaum FR, Eary JF et al (2006a) 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood 107:2184–2191

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pagel JM, Gooley T, Rajendran JG et al (2006b) Targeted radiotherapy using 131I-anti-CD45 antibody followed by allogeneic hematopoietic cell transplantation (HCT): the relationships among dosimetry, bone marrow uptake, and relapse [abstract]. Eur J Nucl Med Mol Imaging 33:S193

    Google Scholar 

  • Pagel JM, Hedin N, Drouet L et al (2008) Eradication of disseminated leukemia in a syngeneic murine leukemia model using pretargeted anti-CD45 radioimmunotherapy. Blood 111:2261–2268

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pagel JM, Gooley TA, Rajendran J et al (2009a) Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood 114:5444–5453

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pagel JM, Matthews DC, Kenoyer A et al (2009b) Pretargeted radioimmunotherapy using anti-CD45 monoclonal antibodies to deliver radiation to murine hematolymphoid tissues and human myeloid leukemia. Cancer Res 69:185–192

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Passegué E, Jamieson CH, Ailles LE et al (2003) Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci U S A 100(Suppl 1):11842–11849

    Article  PubMed Central  PubMed  Google Scholar 

  • Petersdorf S, Kopecky K, Stuart RK et al (2009) Preliminary results of Southwest Oncology Group Study S0106: an international intergroup phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia [abstract #790]. Blood 114:326–327

    Google Scholar 

  • Petti MC, Pinazzi MB, Diverio D et al (2001) Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676). Br J Haematol 115:63–65

    Article  CAS  PubMed  Google Scholar 

  • Pfizer Inc (2010) http://media.pfizer.com/files/products/mylotarg_hcp_letter.pdf. Accessed 23 Jan 2012

  • Pollard JA, Alonzo TA, Loken M et al (2012) Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood 119:3705–3711

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Press OW, Howell-Clark J, Anderson S et al (1994) Retention of B-cell-specific monoclonal antibodies by human lymphoma cells. Blood 83:1390–1397

    CAS  PubMed  Google Scholar 

  • Press OW, Shan D, Howell-Clark J et al (1996) Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells. Cancer Res 56:2123–2129

    CAS  PubMed  Google Scholar 

  • Ravandi F, Estey E, Jones D et al (2009) Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 27:504–510

    Article  CAS  PubMed  Google Scholar 

  • Raza A, Jurcic JG, Roboz GJ et al (2009) Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial. Leuk Lymphoma 50:1336–1344

    Article  CAS  PubMed  Google Scholar 

  • Ricart AD (2011) Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res 17:6417–6427

    Article  CAS  PubMed  Google Scholar 

  • Ringhoffer M, Blumstein N, Neumaier B et al (2005) 188Re or 90Y-labelled anti-CD66 antibody as part of a dose-reduced conditioning regimen for patients with acute leukaemia or myelodysplastic syndrome over the age of 55: results of a phase I-II study. Br J Haematol 130:604–613

    Article  CAS  PubMed  Google Scholar 

  • Rosenblat TL, Mcdevitt MR, Pandit-Taskar N et al (2007) Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-HuM195 (anti-CD33) in acute myeloid leukemia (AML) [abstract #910]. Blood 110:277a

    Google Scholar 

  • Rottinger EM, Bartkowiak D, Bunjes D et al (2003) Enhanced renal toxicity of total body irradiation combined with radioimmunotherapy. Strahlenther Onkol 179:702–707

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Sekeres MA, Lancet JE, Wood BL et al (2013) Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica 98:119–129

    Google Scholar 

  • Sievers EL, Appelbaum FR, Spielberger RT et al (1999) Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 93:3678–3684

    CAS  PubMed  Google Scholar 

  • Sievers EL, Larson RA, Stadtmauer EA et al (2001) Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 19:3244–3254

    CAS  PubMed  Google Scholar 

  • Stasi R, Evangelista ML, Buccisano F et al (2008) Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer Treat Rev 34:49–60

    Article  CAS  PubMed  Google Scholar 

  • Stubbs MC, Armstrong SA (2007) Therapeutic implications of leukemia stem cell development. Clin Cancer Res 13:3439–3442

    Article  CAS  PubMed  Google Scholar 

  • SWOG (2010) http://www.swogstat.org/ROS/ROSBooks/Spring2010/Leukemia.pdf. Accessed 23 Jan 2012

  • Taksin AL, Legrand O, Raffoux E et al (2007) High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia 21:66–71

    Article  CAS  PubMed  Google Scholar 

  • Thomas ED, Storb R, Clift RA et al (1975) Bone-marrow transplantation. N Engl J Med 292:832–843

    Article  CAS  PubMed  Google Scholar 

  • Tsimberidou AM, Giles FJ, Estey E et al (2006) The role of gemtuzumab ozogamicin in acute leukaemia therapy. Br J Haematol 132:398–409

    CAS  PubMed  Google Scholar 

  • Van Der Jagt RH, Badger CC, Appelbaum FR et al (1992) Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. Cancer Res 52:89–94

    CAS  PubMed  Google Scholar 

  • Van Der Velden VH, Te Marvelde JG, Hoogeveen PG et al (2001) Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood 97:3197–3204

    Article  CAS  PubMed  Google Scholar 

  • Walter RB, Pagel JM (2011) Targeted radionuclide therapy for leukemia. In: Speer TW (ed) Targeted radionuclide therapy. Walters Kluwer/Lippincott Williams & Wilkins, Philadelphia, pp 441–457

    Google Scholar 

  • Walter RB, Raden BW, Kamikura DM et al (2005) Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood 105:1295–1302

    Article  CAS  PubMed  Google Scholar 

  • Walter RB, Press OW, Pagel JM (2010) Pretargeted radioimmunotherapy for hematologic and other malignancies. Cancer Biother Radiopharm 25:125–142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Walter RB, Appelbaum FR, Estey EH et al (2012) Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 119:6198–6208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zenz T, Schlenk RF, Glatting G et al (2006) Bone marrow transplantation nephropathy after an intensified conditioning regimen with radioimmunotherapy and allogeneic stem cell transplantation. J Nucl Med 47:278–286

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Medicine/Division of Hematology, University of Washington, 1100 Fairview Ave N, D2-190, 98109-1024, Seattle, WA, USA

    Roland B. Walter MDPhD

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Medicine/ Division of Medical Oncology, University of Washington, 1100 Fairview Ave N, D3-190, 98109-1024, Seattle, WA, USA

    Oliver W. Press MDPhD

  3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, 1100 Fairview Ave N, D2-373, 98109-1024, Seattle, WA, USA

    Irwin D. Bernstein MD

Authors
  1. Roland B. Walter MDPhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oliver W. Press MDPhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irwin D. Bernstein MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland B. Walter MDPhD .

Editor information

Editors and Affiliations

  1. Dept. Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michael Andreeff

Appendices

Conclusion

The clinical studies conducted so far with unconjugated, toxin-loaded, and radiolabeled MoAbs have demonstrated that CD33 and perhaps CD45 and CD66 are valid targets for the treatment of AML. Given this encouraging experience, the use of antibodies is likely expanding significantly in the future with identification of additional AML (stem) cell-associated antigens. However, AML comprises a heterogeneous group of diseases, and antibody-based therapeutics likely only benefit defined patient subsets, as exemplified by the clinical experience with GO. This will pose formidable challenges to the identification of adequate numbers of suitable patients in whom specific therapies can be tested in a controlled fashion.

Acknowledgements

This work was supported by grants P30-CA015704-35S6, P01-CA044991, R01-CA109663, and R01-CA136639 from the National Cancer Institute/National Institutes of Health (NCI/NIH) and a Specialized Center of Research grant (#7008-08) from the Leukemia & Lymphoma Society. R.B.W. is a Leukemia & Lymphoma Scholar in Clinical Research.

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag New York

About this chapter

Cite this chapter

Walter, R., Press, O., Bernstein, I. (2015). Antibody-Based Therapeutics Targeting CD33, CD45, and CD66. In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_27

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1393-0_27

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1392-3

  • Online ISBN: 978-1-4939-1393-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation