Neuroblastoma pp 223-242 | Cite as

Immunology and Immunotherapy

  • Nai-Kong V. Cheung
  • Paul M. Sondel
Part of the Pediatric Oncology book series (PEDIATRICO)


Clin Oncol Cancer Immunol High Risk Neuroblastoma Murine Neuroblastoma Pseudomonas Exotoxin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agus DB, Akita RW, Fox WD et al. (2002) Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2:127–137CrossRefPubMedGoogle Scholar
  2. Allen TM, Sapra P, Moase E et al. (2002) Adventures in targeting. J Liposome Res 12:5–12CrossRefPubMedGoogle Scholar
  3. Amstutz H, Rytz C, Novak-Hofer I et al. (1993) Production and characterization of a mouse/human chimeric antibody directed against human neuroblastoma. Int J Cancer 53:147–152PubMedGoogle Scholar
  4. Barker E, Reisfeld RA (1993) A mechanism for neutrophil-mediated lysis of human neuroblastoma cells. Cancer Res 53:362–367PubMedGoogle Scholar
  5. Batova A, Kamps A, Gillies SD et al. (1999) The ch14.18-GM-CSF fusion protein is effective at mediating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro. Clin Cancer Res 5:4259–4263PubMedGoogle Scholar
  6. Batova A, Strother D, Castleberry RP et al. (2002) Immune response to an anti-idiotype monoclonal antibody 1A7 as a tumor vaccine in children with high risk neuroblastoma. Proc Am Assoc Cancer Res 43:143Google Scholar
  7. Bauer M, Reaman GH, Hank JA et al. (1995) A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin's lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. A Childrens Cancer Group study. Cancer 75:2959–2965PubMedGoogle Scholar
  8. Bauer S, Renner C, Juwana JP et al. (1999) Immunotherapy of human tumors with T-cell-activating bispecific antibodies: stimulation of cytotoxic pathways in vivo. Cancer Res 59:1961–1965PubMedGoogle Scholar
  9. Berthold F, Schumacher R, Schneider A et al. (1989) Removal of neuroblastoma cells from bone marrow by a direct monoclonal antibody rosetting technique. Bone Marrow Transplant 4:273–278PubMedGoogle Scholar
  10. Boerman OC, van Schaijk FG, Oyen WJ et al. (2003) Pretargeted radioimmunotherapy of cancer: progress step by step. J Nucl Med 44:400–411PubMedGoogle Scholar
  11. Bonig H, Laws HJ, Wundes A et al. (2000) In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem cell transplantation in children with solid tumors. Bone Marrow Transplant 26:91–96CrossRefPubMedGoogle Scholar
  12. Bowman L, Grossmann M, Rill D et al. (1998) IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma. Blood 92:1941–1949PubMedGoogle Scholar
  13. Brenner MK, Heslop H, Krance R et al. (2000) Phase I study of chemokine and cytokine gene-modified autologous neuroblastoma cells treatment of relapsed/refractory neuroblastoma using an adenoviral vector. Hum Gene Ther 11:1477CrossRefPubMedGoogle Scholar
  14. Carding SR, Egan PJ (2002) Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2:336–345CrossRefPubMedGoogle Scholar
  15. Carrel F, Amstutz H, Novak-Hofer I et al. (1997) Evaluation of radioiodinated and radiocopper labeled monovalent fragments of monoclonal antibody chCE7 for targeting of neuroblastoma. Nucl Med Biol 24:539–546CrossRefPubMedGoogle Scholar
  16. Carter P (2001) Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 1:118–129CrossRefPubMedGoogle Scholar
  17. Cartron G, Dacheux L, Salles G et al. (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754–758CrossRefPubMedGoogle Scholar
  18. Chari RV, Jackel KA, Bourret LA et al. (1995) Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res 55:4079–4084PubMedGoogle Scholar
  19. Chen S, Caragine T, Cheung NK et al. (2000a) Surface antigen expression and complement susceptibility of differentiated neuroblastoma clones. Am J Pathol 156:1085–1091PubMedGoogle Scholar
  20. Chen S, Caragine T, Cheung NKV et al. (2000b) CD59 expressed on a tumor cell surface modulates decay-accelarating factor expression and enhanses tumor growth in a rat model of human neuroblastoma. Cancer Res 60:3013–3018PubMedGoogle Scholar
  21. Cheung IY, Cheung NKV (1997) Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma. Clin Cancer Res 3:821–826PubMedGoogle Scholar
  22. Cheung IY, Barber D, Cheung NK (1998) Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers. Clin Cancer Res 4:2801–2805PubMedGoogle Scholar
  23. Cheung IY, Lo Piccolo MS, Kushner BH et al. (2003a) Early molecular response in marrow is highly prognostic following treatment with anti-GD2 and GM-CSF. J Clin Oncol 21:3853–3858CrossRefPubMedGoogle Scholar
  24. Cheung IY, Lo Piccolo MS, Kushner BH et al. (2003b) Quantitation of GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction: clinical utility in evaluating adjuvant therapy in neuroblastoma. J Clin Oncol 21:1087–1093CrossRefPubMedGoogle Scholar
  25. Cheung N, Landmeier B, Neely J et al. (1986) Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice. J Natl Cancer Inst 77:739–745PubMedGoogle Scholar
  26. Cheung N, Lazarus H, Miraldi FD et al. (1987) Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 5:1430–1440PubMedGoogle Scholar
  27. Cheung N, Walter EI, Smith-Mensah WH et al. (1988) Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro. J Clin Invest 81:1122–1128PubMedGoogle Scholar
  28. Cheung N, Lazarus H, Miraldi FD et al. (1992) Reassessment of patient response to monoclonal antibody 3F8. J Clin Oncol 10:671–674PubMedGoogle Scholar
  29. Cheung N, Canete A, Cheung IY et al. (1993) Disialoganglioside GD2 anti-idiotypic monoclonal antibodies. Int J Cancer 54:499–505PubMedGoogle Scholar
  30. Cheung N, Cheung IY, Canete A et al. (1994) Antibody response to murine anti-GD2 monoclonal antibodies: correlation with patient survival. Cancer Res 54:2228–2233PubMedGoogle Scholar
  31. Cheung N, Kushner BH, Cheung IY et al. (1998a) Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 16:3053–3060PubMedGoogle Scholar
  32. Cheung N, Kushner BH, Yeh SD et al. (1998b) 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study. Int J Oncol 12:1299–1306PubMedGoogle Scholar
  33. Cheung N, Yu A (2000) Immunotherapy of neuroblastoma. In: Brodeur GM, Sawada T, Tsuchida Y et al. (eds) Neuroblastoma. Elsevier, Philadelphia, pp 541–546Google Scholar
  34. Cheung N, Guo HF, Heller G et al. (2000) Induction of Ab3 and Ab3′ antibody was associated with long-term survival after anti-G(D2) antibody therapy of stage 4 neuroblastoma. Clin Cancer Res 6:2653–2660PubMedGoogle Scholar
  35. Cheung N, Kushner BH, Kramer K (2001a) Monoclonal antibody-based therapy of neuroblastoma. Hematol Oncol Clin North Am 15:853–866CrossRefPubMedGoogle Scholar
  36. Cheung N, Kushner BH, LaQuaglia M et al. (2001b) N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol 36:227–230PubMedGoogle Scholar
  37. Cheung N, Modak S (2002) Oral (1–3,(1–4)-beta-glucan syngergizes with anti-ganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma. Clin Cancer Res 8:1217–1223PubMedGoogle Scholar
  38. Cheung N, Rooney C (2002) Principles of immune and cellular therapy. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology, 4th edn. Lippincott, Philadelphia, pp 381–408Google Scholar
  39. Cheung NK, Guo HF, Modak S et al. (2002) Anti-idiotypic antibody as the surrogate antigen for cloning scFv and its fusion proteins. Hybrid Hybridomics 21:433–443CrossRefPubMedGoogle Scholar
  40. Cheung N, Guo HF, Modak S et al. (2003) Anti-idiotypic antibody facilitates scFv chimeric immune receptor gene transduction and clonal expansion of human lymphocytes for tumor therapy. Hybrid Hybridom 22:209–218CrossRefGoogle Scholar
  41. Cheung N (2004) Therapeutic antibodies and immunologic conjugates. In: Abeloff MD (ed) Clinical oncology. Churchill Livingstone, Edinburgh, pp 661–666Google Scholar
  42. Cheung NK, Modak S, Lin Y, Guo H, Zanzonico P, Chung J, Zuo Y, Sanderson J, Wilbert S, Theodore LJ, Axworthy DB, Larson SM (2004) Single chain Fv-streptavidin substantially improved therapeutic index in multi-step targeting directed at disialoganglioside GD2. J Nucl Med 45:867–877PubMedGoogle Scholar
  43. Colucci F, Caligiuri MA, Santo JP di (2003) What does it take to make a natural killer? Nat Rev Immunol 3:413–425CrossRefPubMedGoogle Scholar
  44. Coze C, Leimig T, Jimeno MT et al. (2001) Retrovirus-mediated gene transfer of the cytokine genes interleukin-1beta and tumor necrosis factor-alpha into human neuroblastoma cells: consequences for cell line behavior and immunomodulatory properties. Eur Cytokine Netw 12:78–86PubMedGoogle Scholar
  45. Cremonesi M, Ferrari M, Chinol M et al. (1999) Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients. Eur J Nucl Med 26:110–120CrossRefPubMedGoogle Scholar
  46. Davidoff AM, Kimbrough SA, Ng CY et al. (1999) Neuroblastoma regression and immunity induced by transgenic expression of interleukin-12. J Pediatr Surg 34:902–907CrossRefPubMedGoogle Scholar
  47. Davis CA, Gillies SA (2003) Immunocytokines: amplification of anti-cancer immunity. Cancer Immunol Immunother 52:297–308PubMedGoogle Scholar
  48. Diefenbach A, Raulet DH (2002) The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev 188:9–21CrossRefPubMedGoogle Scholar
  49. Doubrovina ES, Doubrovin MM, Vider E et al. (2003) Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J Immunol 171:6891–6899PubMedGoogle Scholar
  50. Edwards BS, Nolla HA, Hoffman RR (1992) Resolution of adhesion-and activation-associated components of monoclonal antibody-dependent human NK cell-mediated cytotoxicity. Cell Immunol 144:55–68CrossRefPubMedGoogle Scholar
  51. Enomoto A, Kato K, Yagita H et al. (1997) Adoptive transfer of cytotoxic T lymphocytes induced by CD86-transfected tumor cells suppresses multi-organ metastases of C1300 neuroblastoma in mice. Cancer Immunol Immunother 44:204–210CrossRefPubMedGoogle Scholar
  52. Evans AE, Main E, Zier K et al. (1989) The effects of gamma interferon on natural killer and tumor cells of children with neuroblastoma. A preliminary report. Cancer 64:1383–1387PubMedGoogle Scholar
  53. Evans AE, August CS, Kamani N et al. (1994) Bone marrow transplantation for high risk neuroblastoma at the Children's Hospital of Philadelphia: an update. Med Pediatr Oncol 23:323–327PubMedGoogle Scholar
  54. Favrot MC, Michon J, Floret D et al. (1990) Interleukin 2 immunotherapy in children with neuroblastoma after high-dose chemotherapy and autologous bone marrow transplantation. Pediatr Hematol Oncol 7:275–284PubMedGoogle Scholar
  55. Foon KA, Lutzky J, Baral RN et al. (2000) Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. J Clin Oncol 18:376–384PubMedGoogle Scholar
  56. Friedrich SW, Lin SC, Stoll BR et al. (2002) Antibody-directed effector cell therapy of tumors: analysis and optimization using a physiologically based pharmacokinetic model. Neoplasia 4:449–463CrossRefPubMedGoogle Scholar
  57. Frost JD, Hank JA, Reaman GH et al. (1997) A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma. Cancer 80:317–333CrossRefPubMedGoogle Scholar
  58. Geiger JD, Hutchinson RJ, Hohenkirk LF et al. (2001) Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 61:8513–8519PubMedGoogle Scholar
  59. Goldenberg DM (2003) Advancing role of radiolabeled antibodies in the therapy of cancer. Cancer Immunol Immunother 52:281–296PubMedGoogle Scholar
  60. Goldenberg DM, Chang CH, Sharkey RM et al. (2003) Radioimmunotherapy: Is avidin-biotin pretargeting the preferred choice among pretargeting methods? Eur J Nucl Med Mol Imaging 30:777–780PubMedGoogle Scholar
  61. Goldman A, Vivian G, Gordon I et al. (1984) Immunolocalization of neuroblastoma using radiolabeled monoclonal antibody UJ13A. J Pediatr 105:252–256PubMedGoogle Scholar
  62. Gorter A, Meri S (1999) Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 20:576–582CrossRefPubMedGoogle Scholar
  63. Gutheil JC, Campbell TN, Pierce PR et al. (2000) Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 6:3056–3061PubMedGoogle Scholar
  64. Haight AE, Bowman LC, Ng CY et al. (2000) Humoral response to vaccination with interleukin-2-expressing allogeneic neuroblastoma cells after primary therapy. Med Pediatr Oncol 35:712–715CrossRefPubMedGoogle Scholar
  65. Halin C, Neri D (2001) Antibody-Based targeting of angiogenesis. Crit Rev Ther Drug Carrier Syst 18:299–339PubMedGoogle Scholar
  66. Handgretinger R, Anderson K, Lang P et al. (1995) A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch 14.18 in patients with neuroblastoma. Eur J Cancer 31:261–267CrossRefGoogle Scholar
  67. Handgretinger R, Bruchelt G, Schneider M et al. (1987) Application of interleukin 2 in neuroblastoma. Haematol Blood Transfus 31:116–119PubMedGoogle Scholar
  68. Handgretinger R, Baader P, Dopfer R et al. (1992) A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother 35:199–204CrossRefPubMedGoogle Scholar
  69. Hank JA, Robinson RR, Surfus J et al. (1990) Augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin-2. Cancer Res 50:5234–5239PubMedGoogle Scholar
  70. Hank JA, Surfus JE, Gan J et al. (1996) Activation of human effector cells by a tumor reactive recombinant anti-ganglioside GD2 interleukin-2 fusion protein (ch 14.18-IL2). Clin Cancer Res 2:1951–1959PubMedGoogle Scholar
  71. Heitger A, Ladisch S (1996) Gangliosides block antigen presentation by human monocytes. Biochim Biophys Acta 1303:161–168PubMedGoogle Scholar
  72. Heuer JG, Tucker-McClung C, Hock RA (1999) Neuroblastoma cells expressing mature IL-18, but not proIL-18, induce a strong and immediate antitumor immune response. J Immunother 22:324–335PubMedGoogle Scholar
  73. Hock RA, Reynolds BD, Tucker-McClung CL et al. (1995) Human class II major histocompatibility complex gene transfer into murine neuroblastoma leads to loss of tumorigenicity, immunity against subsequent tumor challenge, and elimination of microscopic preestablished tumors. J Immunother Emphasis Tumor Immunol 17:12–18PubMedGoogle Scholar
  74. Hoefnagel CA, Rutgers M, Buitenhuis CK et al. (2001) A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med 28:359–368CrossRefPubMedGoogle Scholar
  75. Hofheinz RD, Al-Batran SE, Hartmann F et al. (2003) Stromal antigen targeting by a humanised monoclonal antibody: an early phase II Trial of sibrotuzumab in patients with metastatic colorectal cancer. Onkologie 26:44–48CrossRefPubMedGoogle Scholar
  76. Holzer U, Bethge W, Krull F et al. (1995) Superantigen-staphylococcal-enterotoxin-A-dependent and antibody-targeted lysis of GD2-positive neuroblastoma cells. Cancer Immunol Immunother 41:129–136PubMedGoogle Scholar
  77. Houghton AN, Mintzer D, Cordon-Cardo C et al. (1985) Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci USA 82:1242–1246PubMedGoogle Scholar
  78. Huang CS, Utterreuther M, Reisfeld RA (1992) Immunotherapy of GD2+ tumors with a murine monoclonal antibody (MAB) 14G2a; a phase I study. Proc ASCO 11:364Google Scholar
  79. Hugli TE, Muller-Eberhard HJ (1978) Anaphylatoxins: C3a and C5a. Adv Immunol 26:1–53PubMedGoogle Scholar
  80. Ishida H, Matsumura T, Salgaller ML et al. (1996) MAGE-1 and MAGE-3 or-6 expression in neuroblastoma-related pediatric solid tumors. Int J Cancer 69:375–380CrossRefPubMedGoogle Scholar
  81. Jameson J, Witherden D, Havran WL (2003) T-cell effector mechanisms: gammadelta and CD1d-restricted subsets. Curr Opin Immunol 15:349–353CrossRefPubMedGoogle Scholar
  82. Janeway CA, Travers P, Walport M et al. (2001) Immunobiology-5: the immune system in health and disease, 5th edn. Garland Publishing, Taylor and Francis Group, New YorkGoogle Scholar
  83. Juhl H, Petrella EC, Cheung NK et al. (1997) Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells. Immunobiology 197:444–459PubMedGoogle Scholar
  84. Jurcic JG, Larson SM, Sgouros G et al. (2002) Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100:1233–1239PubMedGoogle Scholar
  85. Kawashima I, Tada N, Ikegami S et al. (1988) Mouse monoclonal antibodies detecting disialogangliosides on mouse and human T lymphomas. Int J Cancer 41:267–274PubMedGoogle Scholar
  86. Kemshead JT, Goldman A, Jones D et al. (1985) Therapeutic application of radiolabelled monoclonal antibody UJ13A in children with disseminated neuroblastoma-a phase I study. In: Evans AE, D'Angio GJ, Seeger RC (eds) Advances in neuroblastoma research. Prog Clin Biol Res. Liss, New York, pp 533–544Google Scholar
  87. Kennedy RC, Zhou EM, Lanford RE et al. (1987) Possible role of anti-idiotypic antibodies in the induction of tumor immunity. J Clin Invest 80:1217–1224PubMedGoogle Scholar
  88. Kimberly RP, Wu J, Gibson AW et al. (2002) Diversity and duplicity: human FCgamma receptors in host defense and autoimmunity. Immunol Res 26:177–189CrossRefPubMedGoogle Scholar
  89. King D, Albertini M, Schalch H et al. (2002) Phase I/II trial of the immunocytokine hu14.18-IL2 in patients with metastatic melanoma. Proc Am Soc Clin Oncol 21:16aGoogle Scholar
  90. Koehler G, Milstein C (1975) Continuous culture of fused cells secreting antibody of pre-defined specificity. Nature 256:495–496CrossRefPubMedGoogle Scholar
  91. Koehne G, Guo HF, Trivedi RY et al. (2003) Redirecting NK-cell cytolytic activity to solid tumors using chimeric scFv receptor gene-modified adoptive immunotherapy. Proc Am Soc Clin Oncol 22:175Google Scholar
  92. Kramer K, Gerald WL, Kushner BH et al. (1998) Disialoganglioside G(D2) loss following monoclonal antibody therapy is rare in neuroblastoma. Clin Cancer Res 4:2135–2139PubMedGoogle Scholar
  93. Kramer K, Cheung NK, Humm JL et al. (2000) Targeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8. Med Pediatr Oncol 35:716–718CrossRefPubMedGoogle Scholar
  94. Krause A, Guo HF, Latouche JB et al. (1998) Antigen-dependent CD28 signaling electively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med 188:619–626CrossRefPubMedGoogle Scholar
  95. Kronenberg M, Gapin L (2002) The unconventional lifestyle of NKT cells. Nat Rev Immunol 2:557–568PubMedGoogle Scholar
  96. Kushner BH, Cheung NK (1989) GM-CSF enhances 3F8 monoclonal antibody-dependent cellular cytotoxicity against human melanoma and neuroblastoma. Blood 73:1936–1941PubMedGoogle Scholar
  97. Kushner BH, Cheung NK (1992) Absolute requirement of CD11/ CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity. Blood 79:1484–1490PubMedGoogle Scholar
  98. Kushner BH, Kramer K, Cheung NKV (2001) Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. J Clin Oncol 19:4189–4194PubMedGoogle Scholar
  99. Lammie GA, Cheung NKV, Gerald W et al. (1993) Ganglioside GD2 expression in the human nervous system and in neuroblastomas: an immunohistochemical study. Int J Oncol 3:909–915Google Scholar
  100. Lampson LA, Fisher CA, Whelan JP (1983) Striking paucity of HLA-A, B, C and B2-microglobulin on human neuroblastoma cell lines. J Immunol 130:2471–2478PubMedGoogle Scholar
  101. Larson SM, Pentlow KS, Volkow ND et al. (1991) PET scanning of 124I-3F8 as a novel method of tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. Antibody Immunoconjug Radiopharmaceut 4:34Google Scholar
  102. Larson SM, Divgi C, Sgouros G et al. (2000) Monoclonal antibodies: basic principles — radioisotope conjugates. In: De-Vita VT, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer: principles and practice. Lippincott, Philadelphia, pp 396–412Google Scholar
  103. Lashford L, Jones D, Pritchard J et al. (1987) Therapeutic application of radiolabeled monoclonal antibody UJ13A in children with disseminated neuroblastoma. NCI Monogr 3:53–57PubMedGoogle Scholar
  104. Lashford LS, Davies AG, Richardson RB et al. (1988) A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. Cancer 61:857–868PubMedGoogle Scholar
  105. Li JH, Rosen D, Sondel P et al. (2002) Immune privilege and FasL: two ways to inactivate effector cytotoxic T lymphocytes by FasL-expressing cells. Immunology 105:267–277CrossRefPubMedGoogle Scholar
  106. Li R, Villacreses N, Ladisch S (1995) Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res 55:211–214PubMedGoogle Scholar
  107. Lode HN, Reisfeld RA (2000) Targeted cytokines for cancer immunotherapy. Immunol Res 21:279–288CrossRefPubMedGoogle Scholar
  108. Lode HN, Xiang R, Varki NM et al. (1997) Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst 89:1586–1594CrossRefPubMedGoogle Scholar
  109. Lode HN, Moehler T, Xiang R et al. (1999) Synergy between an antiangiogenic integrin alphav antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases. Proc Natl Acad Sci USA 96:1591–1596CrossRefPubMedGoogle Scholar
  110. Lynch TJ Jr, Lambert JM, Coral F et al. (1997) Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin. J Clin Oncol 15:723–734PubMedGoogle Scholar
  111. Manzke O, Russello O, Leenen C et al. (2001) Immunotherapeutic strategies in neuroblastoma: antitumoral activity of deglycosylated Ricin A conjugated anti-GD2 antibodies and anti-CD3xanti-GD2 bispecific antibodies. Med Pediatr Oncol 36:185–189CrossRefPubMedGoogle Scholar
  112. Marti F, Pardo N, Peiro M et al. (1995) Progression of natural immunity during one-year treatment of residual disease in neuroblastoma patients with high doses of interleukin-2 after autologous bone marrow transplantation. Exp Hematol 23:1445–1452PubMedGoogle Scholar
  113. Masucci G, Ragnhammar P, Wersall P et al. (1990) Granulocytemonocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A). Cancer Immunol Immunother 31:231–235CrossRefPubMedGoogle Scholar
  114. Matthay KK, Seeger RC, Reynolds CP et al. (1994) Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group. J Clin Oncol 12:2382–2389PubMedGoogle Scholar
  115. McDevitt MR, Sgouros G, Finn RD et al. (1998) Radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med 25:1341–1351CrossRefPubMedGoogle Scholar
  116. McGarry RC, Pinto A, Hammersley-Straw DR et al. (1988) Expression of markers shared between human natural killer cells and neuroblastoma lines. Cancer Immunol Immunother 27:47–52CrossRefPubMedGoogle Scholar
  117. Mendelsohn J (2003) Antibody-mediated EGF receptor blockade as an anticancer therapy: from the laboratory to the clinic. Cancer Immunol Immunother 52:342–346PubMedGoogle Scholar
  118. Metelitsa LS, Gillies SD, Super M et al. (2002) Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcgammaRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis. Blood 99:4166–4173CrossRefPubMedGoogle Scholar
  119. Metelitsa LS, Naidenko OV, Kant A et al. (2001) Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J Immunol 167:3114–3122PubMedGoogle Scholar
  120. Michon J, Moutel S, Barbet J et al. (1995a) In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody. Blood 86:1124–1130PubMedGoogle Scholar
  121. Michon J, Perdereau B, Brixy F et al. (1995b) In vivo targeting of human neuroblastoma xenograft by anti-GD2/anti-Fc gamma RI (CD64) bispecific antibody. Eur J Cancer 31A:631–636CrossRefPubMedGoogle Scholar
  122. Miraldi FD, Nelson AD, Kraly C et al. (1986) Diagnostic imaging of human neuroblastoma with radiolabeled antibody. Radiology 161:413–418PubMedGoogle Scholar
  123. Modak S, Kramer K, Gultekin SH et al. (2001) Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Res 61:4048–4054PubMedGoogle Scholar
  124. Moutel S, Birkle S, Laurence V et al. (1997) Generation and characterization of a mouse single-chain antibody fragment specific for disialoganglioside (GD2). Hybridoma 16:335–346PubMedGoogle Scholar
  125. Mujoo K, Reisfeld RA, Cheung L et al. (1991) A potent and specific immunotoxin for tumor cells expressing disialoganglioside GD2. Cancer Immunol Immunother 34:198–204CrossRefPubMedGoogle Scholar
  126. Munn DH, Cheung NK (1987) Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity (ADCC) against human melanoma. Cancer Res 47:6600–6605PubMedGoogle Scholar
  127. Murray JL, Cunningham JE, Brewer H et al. (1994) Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 12:184–193PubMedGoogle Scholar
  128. Nakamura K, Tanaka Y, Shitara K et al. (2001) Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions. Cancer Immunol Immunother 50:275–284PubMedGoogle Scholar
  129. Neal ZC, Imboden M, Rakhmilevich AL et al. (2003) Recurrent murine neuroblastomas increase or decrease MHC class I expression to escape NK-or T cell dependent immune destruction. Cancer Immunol Immunother 53:41–52CrossRefPubMedGoogle Scholar
  130. Novak-Hofer I, Honer M, Ametamey S et al. (2003) Imaging of renal carcinoma xenografts with (64)Cu-labelled anti-L1-CAM antibody chCE7. Eur J Nucl Med Mol Imaging 30:1066CrossRefPubMedGoogle Scholar
  131. Ohta S, Igarashi S, Honda A et al. (1993) Cytotoxicity of adriamycin-containing immunoliposomes targeted with antiganglioside monoclonal antibodies. Anticancer Res 13:331–336PubMedGoogle Scholar
  132. Ollert MW, David K, Schmitt C et al. (1996) Normal human serum contains a natural IgM antibody cytotoxic for human neuroblastoma cells. Proc Natl Acad Sci USA 93:4498–4503CrossRefPubMedGoogle Scholar
  133. Ottonello L, Epstein AL, Dapino P et al. (1999) Monoclonal Lym-1 antibody-dependent cytolysis by neutrophils exposed to granulocyte-macrophage colony-stimulating factor: intervention of FcgammaRII (CD32), CD11b-CD18 integrins, and CD66b glycoproteins. Blood 93:3505–3511PubMedGoogle Scholar
  134. Ozkaynak MF, Sondel PM, Krailo MD et al. (2000) Phase I study of chimeric human/murine antiganglioside GD2 monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma inmmediately after hematopoietic stem-cell transplantation: a Children's Cancer Group Study. J Clin Oncol 18:4077–4085PubMedGoogle Scholar
  135. Paganelli G, Bartolomei M, Ferrari M et al. (2001) Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results. Cancer Biother Radiopharm 16:227–235CrossRefPubMedGoogle Scholar
  136. Passoni L, Scardino A, Bertazzoli C et al. (2002) ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes. Blood 99:2100–2106CrossRefPubMedGoogle Scholar
  137. Pastan I (2003) Immunotoxins containing Pseudomonas exotoxin A: a short history. Cancer Immunol Immunother 52:338–341PubMedGoogle Scholar
  138. Pertl U, Luster AD, Varki NM et al. (2001) IFN-gamma-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy. J Immunol 166:6944–6951PubMedGoogle Scholar
  139. Pertl U, Wodrich H, Ruehlmann JM et al. (2003) Immunotherapy with a posttranscriptionally modified DNA vaccine induces complete protection against metastatic neuroblastoma. Blood 101:649–654CrossRefPubMedGoogle Scholar
  140. Pession A, Prete A, Locatelli F et al. (1998) Immunotherapy with low-dose recombinant interleukin 2 after high-dose chemotherapy and autologous stem cell transplantation in neuroblastoma. Br J Cancer 78:528–533PubMedGoogle Scholar
  141. Philip T, Ladenstein R, Lasset C et al. (1997) 1070 myeloablative megatherapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions. European Group for Blood and Marrow Transplant Registry Solid Tumour Working Party. Eur J Cancer 33:2130–2135CrossRefPubMedGoogle Scholar
  142. Podoloff JL, Murray JL, Bhadkamkar VA et al. (1991) Radioimmunolocalization (RIL) of an anti-ganglioside antibody directed against GD2 ganglioside: imaging considerations. J Nucl Med 32:970Google Scholar
  143. Posey JA, Ng TC, Yang B et al. (2003) A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma. Clin Cancer Res 9:1323–1332PubMedGoogle Scholar
  144. Presta LG, Chen H, O'Connor SJ et al. (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMedGoogle Scholar
  145. Prewett M, Huber J, Li Y et al. (1999) Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 59:5209–5218PubMedGoogle Scholar
  146. Raffaghello L, Pagnan G, Pastorino F et al. (2003) In vitro and in vivo antitumor activity of liposomal Fenretinide targeted to human neuroblastoma. Int J Cancer 104:559–567CrossRefPubMedGoogle Scholar
  147. Raffaghello L, Airoldi I, Prigione I et al. (2004) Functional expression and release of ligands for the activating immunoreceptor NKG2D in human neuroblastoma. Adv Neuroblast Res 11th abstract #202.1Google Scholar
  148. Ragupathi G, Livingston P, Hood C et al. (2003) Immunogenicity of GD2 lactone (GD2L)-KLH conjugate plus immunological adjuvant QS-21 vaccine in patients wtih melanoma. Clin Cancer Res 9:5214–5220PubMedGoogle Scholar
  149. Ravetch JV, Bolland S (2001) IgG Fc receptors. Annu Rev Immunol 19:275–290CrossRefPubMedGoogle Scholar
  150. Reiter Y (2001) Recombinant immunotoxins in targeted cancer cell therapy. Adv Cancer Res 81:93–124PubMedGoogle Scholar
  151. Roguska MA, Pedersen JT, Henry AH et al. (1996) A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing. Protein Eng 9:895–904PubMedGoogle Scholar
  152. Ross GD, Vetvicka V, Yan J et al. (1999) Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology 42:61–74CrossRefPubMedGoogle Scholar
  153. Rossig C, Bollard CM, Nuchtern JG et al. (2001) Targeting of G(D2)-positive tumor cells by human T lymphocytes engineered to express chimeric T-cell receptor genes. Int J Cancer 94:228–236CrossRefPubMedGoogle Scholar
  154. Rousseau RF, Haight AE, Hirschmann-Jax C et al. (2003) Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma. Blood 101:1718–1726CrossRefPubMedGoogle Scholar
  155. Sandler AD, Chihara H, Kobayashi G et al. (2003) CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma. Cancer Res 63:394–399PubMedGoogle Scholar
  156. Sarkar AK, Nuchtern JG (2000) Lysis of MYCN-amplified neuroblastoma cells by MYCN peptide-specific cytotoxic T lymphocytes. Cancer Res 60:1908–1913PubMedGoogle Scholar
  157. Satoh J, Kurohara K, Yukitake M et al. (1998) Interleukin-15, a T-cell growth factor, is expressed in human neural cell lines and tissues. J Neurol Sci 155:170–177CrossRefPubMedGoogle Scholar
  158. Scanlan MJ, Gure AO, Jungbluth AA et al. (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188:22–32CrossRefPubMedGoogle Scholar
  159. Scheffold C, Kornacker M, Scheffold YC et al. (2002) Visualization of effective tumor targeting by CD8+ natural killer T cells redirected with bispecific antibody F(ab')(2) HER2xCD3. Cancer Res 62:5785–5791PubMedGoogle Scholar
  160. Schilbach KE, Geiselhart A, Wessels JT et al. (2000) Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells. J Immunother 23:536–548CrossRefPubMedGoogle Scholar
  161. Schonmann SM, Iyer J, Laeng H et al. (1986) Production and characterization of monoclonal antibodies against human neuroblastoma. Int J Cancer 37:255–262PubMedGoogle Scholar
  162. Schulz G, Cheresh DA, Varki NM et al. (1984) Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 44:5914–5920PubMedGoogle Scholar
  163. Scott AM, Lee FT, Hopkins W et al. (2001) Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial. J Clin Oncol 19:3976–3987PubMedGoogle Scholar
  164. Sen G, Chakraborty M, Foon KA et al. (1998) Induction of IgG antibodies by an anti-idiotype antibody mimicking disialoganglioside GD2. J Immunother 21:75–83PubMedGoogle Scholar
  165. Shen W, Ladisch S (2002) Ganglioside GD1a impedes lipopolysaccharide-induced maturation of human dendritic cells. Cell Immunol 220:125–133CrossRefPubMedGoogle Scholar
  166. Shimizu M, Fontana A, Takeda Y et al. (1999) Induction of antitumor immunity with Fas/APO-1 ligand (CD95L)-transfected neuroblastoma neuro-2a cells. J Immunol 162:7350–7357PubMedGoogle Scholar
  167. Shimizu T, Berhanu A, Redlinger RE Jr et al. (2001) Interleukin-12 transduced dendritic cells induce regression of established murine neuroblastoma. J Pediatr Surg 36:1285–1292CrossRefPubMedGoogle Scholar
  168. Shurin GV, Gerein V, Lotze MT et al. (1998) Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand. Nat Immun 16:263–274CrossRefPubMedGoogle Scholar
  169. Shurin GV, Shurin MR, Bykovskaia S et al. (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369PubMedGoogle Scholar
  170. Siapati KE, Barker S, Kinnon C et al. (2003) Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12. Br J Cancer 88:1641–1648CrossRefPubMedGoogle Scholar
  171. Smolarz K, Waters W, Sieverts H et al. (1989) Immunoscintigraphy with Tc-99m-labeled monoclonal antibody BW575 compared with I-123 MIBG scintigraphy in neuroblastoma. Radiology 173:152–153Google Scholar
  172. Smyth MJ, Crowe NY, Hayakawa Y et al. (2002) NKT cells: conductors of tumor immunity? Curr Opin Immunol 14:165–171CrossRefPubMedGoogle Scholar
  173. Soling A, Schurr P, Berthold F (1999) Expression and clinical relevance of NY-ESO-1,MAGE-1 and MAGE-3 in neuroblastoma. Anticancer Res 19:2205–2209PubMedGoogle Scholar
  174. Sondel PM, Hank JA (1997) Combination therapy with interleukin-2 and antitumor monoclonal antibodies. Cancer J Sci Am 3(Suppl 1):S121–S127PubMedGoogle Scholar
  175. Tai T, Cahan LD, Paulson JC et al. (1984) Human monoclonal antibody against ganglioside GD2: use in development of enzyme-linked immunosorbent assay for the monitoring of anti-GD2 in cancer patients. J Natl Cancer Inst 73:627–633PubMedGoogle Scholar
  176. Takamizawa S, Okamoto S, Wen J et al. (2000) Overexpression of Fas-ligand by neuroblastoma: a novel mechanism of tumor-cell killing. J Pediatr Surg 35:375–379CrossRefPubMedGoogle Scholar
  177. Thomas PB, Delatte SJ, Sutphin A et al. (2002) Effective targeted cytotoxicity of neuroblastoma cells. J Pediatr Surg 37:539–544CrossRefPubMedGoogle Scholar
  178. Todo T, Martuza RL, Dallman MJ et al. (2001) In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity. Cancer Res 61:153–161PubMedGoogle Scholar
  179. Toren A, Nagler A, Rozenfeld-Granot G et al. (2000) Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma. Transplantation 70:1100–1104CrossRefPubMedGoogle Scholar
  180. Tsao CY, Lou W, Wang S et al. (2002) Identification of GD2 ganglioside peptide mimics by using phage display peptide libraries. Proc Am Assoc Cancer Res 43:280Google Scholar
  181. Tur MK, Sasse S, Stocker M et al. (2001a) An anti-GD2 single chain Fv selected by phage display and fused to Pseudomonas exotoxin A develops specific cytotoxic activity against neuroblastoma derived cell lines. Int J Mol Med 8:579–584PubMedGoogle Scholar
  182. Tur MK, Huhn M, Sasse S et al. (2001b) Selection of scFv phages on intact cells under low pH conditions leads to a significant loss of insert-free phages. Biotechniques 30:404–408, 410, 412–413PubMedGoogle Scholar
  183. Turner JG, Rakhmilevich AL, Burdelya L et al. (2001) Anti-CD40 antibody induces antitumor and antimetastatic effects: the role of NK cells. J Immunol 166:89–94PubMedGoogle Scholar
  184. Vaickus L, Biddle W, Cemerlic D et al. (1990) Interferon gamma augments Lym-1-dependent, granulocyte-mediated tumor cell lysis. Blood 75:2408–2416PubMedGoogle Scholar
  185. Valteau-Couanet D, Leboulaire C, Maincent K et al. (2002) Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients. Blood 100:2554–2561CrossRefPubMedGoogle Scholar
  186. Van der Bruggen P, Zhang Y, Chaux P et al. (2002) Tumor-specific shared antigenic peptides recognized by human T cells. Immunol Rev 188:51–64CrossRefPubMedGoogle Scholar
  187. Van Spriel AB, van Ojik HH, van de Winkel JG (2000) Immunotherapeutic perspective for bispecific antibodies. Immunol Today 21:391–397CrossRefPubMedGoogle Scholar
  188. Vlk V, Eckschlager T, Kavan P et al. (2000) Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients. Pediatr Hematol Oncol 17:31–44CrossRefPubMedGoogle Scholar
  189. Wargalla UC, Reisfeld RA (1989) Rate of internalization of an immunotoxin correlates with cytotoxic activity against human tumor cells. Proc Natl Acad Sci USA 86:5146–5150PubMedGoogle Scholar
  190. Wigginton JM, Wiltrout RH (2002) IL-12/IL-2 combination cytokine therapy for solid tumours: translation from bench to bedside. Exp Opin Biol Ther 2:513–524CrossRefGoogle Scholar
  191. Wu DY, Segal NH, Sidobre S et al. (2003) Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells. J Exp Med 198:173–181CrossRefPubMedGoogle Scholar
  192. Xiao W-h, Yu A, Sorkin LS (1997) Electrophysiological characteristics of primary afferent fibers after systemic administration of anti-GD2 ganglioside antibody. Pain 69:145–151CrossRefPubMedGoogle Scholar
  193. Yeh SD, Larson SM, Burch L et al. (1991) Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine (MIBG) and standard diagnostic modalities. J Nucl Med 32:769–776PubMedGoogle Scholar
  194. Yoshida H, Tanabe M, Miyauchi M et al. (1999) Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors. Cancer Gene Ther 6:395–401CrossRefPubMedGoogle Scholar
  195. Yu AL, Batova A, Alvarado C, Rao VJ, Castelberry RP (1997) Usefulness of a chimeric anti-GD2 (ch.14.18) and GM-CSF for refractory neuroblastoma: a POG phase II study. Proc ASCO 16:1846Google Scholar
  196. Yu A, Uttenreuther-Fischer M, Huang C-S et al. (1998) Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 16:2169–2180PubMedGoogle Scholar
  197. Yuki N, Yamada M, Tagawa Y et al. (1997) Pathogenesis of the neurotoxicity caused by anti-GD2 antibody therapy. J Neurol Sci 149:127–130CrossRefPubMedGoogle Scholar
  198. Zalutsky MR, Vaidyanathan G (2000) Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alphaparticle radiotherapy. Curr Pharm Des 6:1433–1455CrossRefPubMedGoogle Scholar
  199. Zeytin HE, Tripathi PK, Bhattacharya-Chatterjee M et al. (2000) Construction and characterization of DNA vaccines encoding the single-chain variable fragment of the anti-idiotype antibody 1A7 mimicking the tumor-associated antigen disialoganglioside GD2. Cancer Gene Therapy 7:1426–1436CrossRefPubMedGoogle Scholar
  200. Zhu Z, Hattori K, Zhang H et al. (2003) Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity. Leukemia 17:604–611CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Nai-Kong V. Cheung
  • Paul M. Sondel

There are no affiliations available

Personalised recommendations