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Antibody-based immunotherapy in high-risk neuroblastoma

  • Erik Johnson (a1), Shannon M. Dean (a2) and Paul M. Sondel (a3)

Although great advances have been made in the treatment of low- and intermediate-risk neuroblastoma in recent years, the prognosis for advanced disease remains poor. Therapies based on monoclonal antibodies that specifically target tumour cells have shown promise for treatment of high-risk neuroblastoma. This article reviews the use of monoclonal antibodies either as monotherapy or as part of a multifaceted treatment approach for advanced neuroblastoma, and explains how toxins, cytokines, radioactive isotopes or chemotherapeutic drugs can be conjugated to antibodies to enhance their effects. Tumour resistance, the development of blocking antibodies, and other problems hindering the effectiveness of monoclonal antibodies are also discussed. Future therapies under investigation in the area of immunotherapy for neuroblastoma are considered.

Corresponding author
*Corresponding author: Paul M. Sondel, Departments of Pediatrics, Human Oncology and Genetics and University of Wisconsin Paul P. Carbone Cancer Center, The University of Wisconsin-Madison, K4/448 600 Highland Avenue, Madison, WI 53792, USA. Tel: +1 608 263 9069; Fax: +1 608 263 4226; E-mail:
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1Cheung, N.K., Kushner, B.H. and Kramer, K. (2001) Monoclonal antibody-based therapy of neuroblastoma. Hematol Oncol Clin North Am 15, 853-866
2Cheung, N.K. et al. (1997) Treatment of advanced stage neuroblastoma. In Principles and Practice of Genitourinary Oncology (Reghavan, D., ed.), pp. 1101-1111, Lippincott, Williams, and Wilkins
3Ater, J.L. (2004) Neuroblastoma. In Behrman: Nelson Textbook of Pediatrics (17th edn) (Behrman, R.E., Kliegman, R.M. and Jenson, H.A., eds), pp. 1709-1711, Saunders
4Schmidt, M.L. et al. (2000) Biologic factors determine prognosis in infants with stage IV neuroblastoma. A prospective Children's Cancer Group study. J Clin Oncol 18,1260-1268
5Kushner, B.H. et al. (1994) Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age. J Clin Oncol 12, 2607-2613
6Matthay, K.K. et al. (1999) Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med 341,1165-1173
7Berthold, F. et al. (2005) Myeloablative megatherapy with autologous stem cell resuce versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomized controlled trial. Lancet Oncol 6, 649-658
8Franks, L.M. et al. (1997) Neuroblastoma in adults and adolescents: An indolent course with poor survival. Cancer 79, 2028-2035
9Sondel, P.M. and Hank, J.A. (2001) Antibody-directed, effector cell-mediated tumor destruction. Hematol Oncol Clin North Am 15, 703-721
10Stephenson, J. (1995) Reengineered mononclonal antibodies step up to the plate in cancer studies. JAMA 274, 1821-1822
11Sondel, P.M. et al. (2003) Preclinical and clinical development of immunocytokines. Curr Opin Investig Drugs 4, 696-700
12Jurcic, J.G., Scheinberg, D.A. and Houghton, A.N. (1997) Monoclonal antibody therapy of cancer. Cancer Chemother Biol Resp Mod 17, 195-216
13Moss, T.J. et al. (1991) Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma. N Engl J Med 324, 219-226
14Seeger, R.C. et al. (2000) Quantitative tumor cell content of bone marrow and blood as a predictor of outcome in stage IV neuroblastoma: a Children's Cancer Group study. J Clin Oncol 18, 4067-4076
15Colucci, F., Caligiuri, M.A. and Santo, J.P. (2003) What does it take to make a natural killer cell? Nat Rev Immunol 3, 413-425
16Cheung, N.K. and Sondel, P.M. (2005) Neuroblastoma immunology and immunotherapy. In Neuroblastoma (Cohn, S. and Cheung, N.K., eds), pp. 223-242, Springer Press
17Cheung, N.K. et al. (1987) Ganglioside GD2 specific monoclonal antibody 3F8- a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 5, 1430-1440
18Mujoo, K. et al. (1987) Disialoganglioside GD2 on human neuroblastoma cells: Target antigen for monoclonal antibody mediated cytolysis and suppression of tumor growth. Cancer Res 47, 1098-1104
19Svennerholm, L. et al. (1994) Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord. Biochem Biophys Acta 1214, 115-123
20Schulz, G. et al. (1984) Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma. Cancer Res 44, 5914-5920
21Nadler, L.M. et al. (1981) Diagnosis and treatment of human leukemias and lymphomas utilizing monoclonal antibodies. Prog Hematol 12,187-225
22Kramer, K. et al. (1998) Disialoganglioside GD2 loss following monoclonal antibody therapy is rare in neuroblastoma. Clin Cancer Res 4, 2135-2139
23Kushner, B.H. et al. (2002) Curability of recurrent disseminated disease after surgery alone for local-regional neuroblastoma using intensive chemotherapy and anti-GD2 immunotherapy. J Pediatr Hematol Oncol 25, 515-519
24Cheung, N.K. and Modak, S. (2002) Oral (1–3), (1–4)-B-D-Glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the treatment of neuroblastoma. Clin Can Res 8, 1217-1223
25Sondel, P.M. and Gillies, S.D. (2002) Immunocytokines for Cancer Immunotherapy. In Handbook of Cancer Vaccines. (Morse, M.A., Clay, T.M. and Lyerly, H.K., eds), pp. 341-358, Humana Press
26Yeh, S.D. et al. (1991) Radioimmunodetection of neuroblastoma with iodine-131–3F8: Correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. J Nucl Med 32, 769-776
27Cheung, N.K. et al. (1998) 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study. Int J Oncol 12, 1299-1306
28Cheung, N.K. (2000) Monoclonal antibody-based therapy for neuroblastoma. Curr Oncol Rep 2(6), 547-553
29Cheung, I.Y. et al. (2003) Early molecular response in marrow is highly prognostic following treatment with anti-GD2 and GM-CSF. JCO 21, 3853-3858
30Chueng, I.Y. et al. (2003) Quantitations of GD2 synthase mRNA by real time reverse transcriptase polymerase chain reaction: clinical utility in evaluating adjuvant therapy in neuroblastoma. J Clin Oncol 21, 1087-1093
31Lammie, G.A. et al. (1993) Ganglioside GD2 expression in the human nervous system and in neuroblastomas: an immunohistochemical study. Int J Oncol 3, 909-915
32Xiao, W.H., Yu, A. and Sorkin, L.S. (1997) Electrophysiological characteristics of primary afferent fibers after systemic administration of anti-GD2 ganglioside antibody. Pain 69, 145-151
33Yuki, N. et al. (1997) Pathogenesis of the neurotoxicity caused by anti-GD antibody therapy. J Neurol Sci 149, 127-130
34Kushner, B.H., Kramer, K. and Cheung, N.K. (2001) Phase II trial of the anti-GD2 monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. J Clin Oncol 19, 4189-4194
35Cheung, N.K. et al. (1988) Decay-accelerating factor protects human tumor cells from compelement-mediated cytotoxicity in vitro. J Clin Invest 81, 1122-1128
36Kushner, B.H. and Cheung, N.K. (1989) GM-CSF enhances 3F8 monoclonal antibody-dependent cellular cytotoxicity against human melanoma and neuroblastoma. Blood 73, 19361941
37Chen, S. et al. (2000) Surface antigen expression and complement susceptibility of differentiated neuroblastoma clones. Am J Pathol 156, 1085-1091
38Mujoo, K. et al. (1989) Functional properties and effects on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18. Cancer Res 49, 2857-2861
39Saarinen, U.M. et al. (1985) Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: Method for purging autologous bone marrow. Cancer Res 45, 5969
40Munn, D.H. and Cheung, N.K. (1987) Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity against human melanoma. Cancer Res 47, 6600-6605
41Barker, E. et al. (1991) Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Research 51, 144-149
42Handgretinger, R. et al. (1992) A Phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother 35, 199-204
43Murray, J.L. et al. (1994) Phase I trial of murine monoclonal antibody 14.G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 12, 184-193
44Saleh, M.N. et al. (1992) Phase I trial of the murine monoclonal anti-GD antibody 14.G2a in metastatic melanoma. Cancer Res 52, 4342-4347
45Handgretinger, R. et al. (1995) A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 31A, 261-267
46Yu, A.L. 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, 2169-2180
47Uttenreuther-Fischer, M.M., Huang, C.S. and Yu, A.L. (1995) Pharmacokinetics of human-mouse chimeric anti-GD2 mAb ch14.18 in a phase I trial in neuroblastoma patients. Cancer Immunol Immunother 41, 331-338
48Hank, J.A. et al. (1990) Augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin-2. Cancer Res 50, 5234-5239
49Barker, E. et al. (1991) Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 51, 144-149
50Furman, W.L. et al. (1991) Therapeutic effects and pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy. J Clin Oncol 9, 1022-1028
51Baldwin, G.C. et al. (1993) Colony stimulating factor enhancement of myeloid effector cell cytotoxicity towards neuroectodermal tumor cells. Br J Haematol 83, 545-553
52Metelitsa, L.S. et al. (2002) Antidisialogangloside/ granulocyte macrophage-colony stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on Fc gamma RII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis. Blood 99, 4166-4173
53Ozkaynak, M.F. et al. (2000) A Phase I study of ch14.18 with GM-CSF in children with neuroblastoma immediately after hematopoietic stem cell transplantation. Children's Cancer Group Study. J Clin Oncol 18, 4077-4085
54Frost, J.D. et al. (1997) A Phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus Interleukin-2 in children with refractory neuroblastoma: a report of the Children's Cancer Group. Cancer 80, 317-333
55Sondel, P.M. et al. (1986) Destruction of autologous human lymphocytes by IL2 activated cytotoxic cells. J Immunol 137, 502-511
56Mule, J. et al. (1987) Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high dose recombinant interleukin-2. J Immunol 139, 285-295
57Sondel, P.M. and Hank, J.A. (1997) Combination therapy with interleukin-2 and antitumor monoclonal antibodies. Cancer J Sci Am 3, S121-127
58Hank, J.A., Albertini, M.R. and Sondel, P.M. (1999) Monoclonal antibodies, cytokines and fusion proteins in the treatment of malignant disease. In Cancer Chemotherapy and Biological Response Modifiers Annual 18 (Pinedo, H.M., Longo, D.L. and Chabner, B.A., eds), pp. 210-222, Elsevier Science
59Hank, J.A. (1994) Treatment of neuroblastoma patients with antiganglioside GD2 antibody plus interleukin-2 induces antibody dependent cellular cytotoxicity against neuroblastoma detected in vitro. J Immunother 15, 29-37
60Xia, Y. et al. (1999) The β-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J Immunol 162, 2281-2290
61Vetvicka, V., Thornton, B.P. and Ross, G.D. (1997) Targeting of natural killer cells to mammary carcinoma via naturally occurring tumor cell-bound iC3b and β-glucan primed CR3 (CD11b/CD18). J Immunol 159, 599-605
62Di Renzo, L., Yefenof, E. and Klein, E. (1991) The function of human NK cells is enhanced by β-glucan, a ligand of CR3 (CD11b/CD18). Eur J Clin Nutr 21, 1755-1758
63Vetvicka, V., Thornton, B.P. and Ross, G.D. (1996) Soluble β-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest 98, 50-61
64Czop, J.K. and Austen, K.F. (1985) Properties of glycans that activate the human alternative complement pathway and interact with the human monocyte β-glucan receptor. J Immunol 135, 3388-3393
65Thornton, B.P. et al. (1996) Analysis of the sugar specificity and molecular location of the β-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol 156, 1235-1246
66Hong, F. et al. (2004) Mechanism by which orally administered B-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol 173, 797-806
67Cheung, N.K. et al. (2002) Orally administered beta-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol Immunother 51, 557-564
68Manzke, O. 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, 185-189
69Tur, M.K. et al. (2001) An anti-GD2 single chain Fv selected by phage display and fused to Pseudomonas exotoxin A develops specific cytotoxicity against neuroblastoma derived cell lines. Int J Mol Med 8, 579-584
70Thomas, P.B. et al. (2002) Effective targeted cytotoxicity of neuroblastoma Cells. J Pediatr Surg 37, 539-544
71Juhl, H. et al. (1997) Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells. Immunobiology 197, 444-459
72Holzer, U. et al. (1995) Superantigen-staphylococcal-enterotoxin A-dependent and antibody-targeted lysis of GD2-positive neuroblastoma cells. Cancer Immunol Immunother 41, 129-136
73Ohta, S. et al. (1993) Cytotoxicity of adriamycin-containing immunoliposomes targeted with anti-ganglioside monoclonal antibodies. Anticancer Res 13, 331-336
74Raffaghello, L. et al. (2003) In vitro and in vivo antitumor activity of liposomal fenretinide targeted to human neuroblastoma. Int J Cancer 104, 559-567
75Reuland, P. et al. (2001) Follow-up in neuroblastoma: comparison of metaiodobenzylguanidine and a chimeric anti-GD2 antibody for detection of tumor relapse and therapy response. J Pediatr Hematol Oncol 23, 437-444
76Goldman, A. et al. (1984) Immunolocalization of neuroblastoma using radiolabeled monoclonal antibody UJ13A. J Pediatr 105, 252-256
77Berthold, F. et al. (1990) Immunoscintigraphic imaging of mIBG-negative metastases in neuroblastoma. Am J Pediatr Hematol Oncol 12, 61-62
78Carrel, F. et al. (1997) Evaluation of radioiodinated and radiocopper labeled monovalent fragments of monoclonal antibody chCE7 for targeting of neuroblastoma. Nucl Med Biol 24, 539-546
79Modak, S. and Cheung, N.K. (2005) Antibody based targeted radiation to pediatric tumors. J Nucl Med 46, 157S-163S
80Cheung, N.K. et al. (2001) N7: a novel multi-modality therapy of high-risk neuroblastoma in children diagnosed over 1 year of age. Med Pediatr Oncol 36, 227-230
81Kramer, K. et al. (2001) Neuroblastoma metastatic to the central nervous system: The Memorial Sloan-Kettering Cancer Center experience and a literature review. Cancer 91, 1510-1519
82Barmada, M.A. et al. (1999) Treatment of neoplastic meningeal xenografts by intraventricular administration of an anti-ganglioside monoclonal antibody 3F8. Int J Cancer 82, 538-548
83Bergman, I. et al. (1999) Intrathecal administration of an antiganglioside antibody results in specific accumulation within meningeal neoplastic xenografts in nude rats. J Immunother 22, 114-123
84Kramer, K. et al. (2000) Targeted radioimmunotherapy for leptomeningeal cancer using I131-3F8. Med Pediatr Oncol 35, 716-718
85Modak, S. et al. (2001) Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Res 61, 4048-4054
86Lode, H.N. et al. (1998) Immunocytokines: a promising approach to cancer immunotherapy. Pharmacol Ther 80, 277-292
87Gillies, S.D. et al. (1993) Biological activity and in vivo clearance of antitumor antibody/cytokine fusion proteins. Bioconjugate Chem 4, 230-235
88Gan, J. et al. (1999) Specific ELISA systems for quantitation of antibody-cytokine fusion proteins. Clin Diagn Lab Immunol 6, 236-242
89Gillies, S.D. et al. (1992) Antibody-targeted interleukin 2 stimulates the T-cell killing of autologous tumor cells. Proc Natl Acad Sci U S A 89, 1428-1432
90Weil-Hillman, G. et al. (1989) Lymphokine-activated killer activity induced by in vivo interleukin 2 therapy: predominant role for lymphocytes with increased expression of CD2 and Leu19 antigens but negative expression of CD16 antigens. Cancer Res 49, 3680-3688
91Voss, S.D. et al. (1990) Increased expression of the interleukin 2 (IL2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL2 therapy: p70 expression does not alone predict the level of intermediate affinity IL2 binding. J Exp Med 172, 1101-1114
92Hank, J.A. et al. (1996) Activation of human effector cells by a tumor reactive recombinant anti-ganglioside-GD2/ interleukin-2 fusion protein (ch14.18-IL2). Clin Cancer Res 2, 1951-1959
93Lode, H.N. et al. (1997) Targeted interleukin-2 therapy of spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst 89, 1586-1594
94Lode, H.N. et al. (1998) Natural killer cell mediated eradication of neuroblastoma metastases to bone marrow by targeted IL2 therapy. Blood 91, 1706-1715
95Osenga, K.L. et al. (2006) A Phase I clinical trial of hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res 12, 1750-1759
96Batova, A. 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, 4259-4263
97Klingebiel, T. et al. (1998) Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high dose chemotherapy and immunotherapy: A pilot study. Eur J Cancer 34, 1398-1402
98Simon, T. et al. (2004) Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol 22, 3549-3557
99Simon, T. et al. (2005) Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody ch14.18 consolidation therapy. Klin Padiatr 217(3), 147-152
100Kushner, B.K. et al. (2004) Camptothecin Analogs (Irinotecan or Topotecan) plus high-dose cyclophosphamide as preparative regimens for antibody-based immunotherapy in resistant neuroblastoma. Clin Canc Res 10, 84-87
101Heslop, H.E. et al. (1996) Use of gene marking in bone marrow transplantation. Cancer Detect Prev 20, 108-113
102Yeager, A.M. et al. (1986) Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N Engl J Med 315, 141-147
103Beaujean, F. et al. (1989) Hematopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow. Bone Marrow Transplant 4, 537-541
104Gulati, S. et al. (1990) Photoradiation methods for purging autologous bone marrow grafts. Prog Clin Biol Res 333, 87-102
105Meck, M.M. et al. (2001) A virus-directed enzyme prodrug therapy approach to purging neuroblastoma cells from hematopoietic cells using adenovirus encoding rabbit carboxylesterase and CPT-11. Cancer Res 61, 5083-5089
106Cheung, I.Y. et al. (2002) Quantitation of GD2 synthase mRNA by real-time reverse transcription-polymerase chain reaction: utility in bone marrow purging of neuroblastoma by anti-GD2 antibody 3F8. Cancer 94, 3042-3048
107Donovan, J. et al. (2000) CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol 35, 677-682
108Handgretinger, R. et al. (2003) Tumour cell contamination of autologous stem cell grafts in high-risk neuroblastoma: the good news? Br J Cancer 88, 1874-1877
109Neal, Z.C. et al. (2004) NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother 53, 41-52
110Imboden, M. et al. (2001) The level of MHC class I expression on murine adenocarcinoma can change the antitumor effector mechanism of immunocytokine therapy. Cancer Res 61, 1500-1507
111Neal, Z.C. et al. (2007) Flt3-L gene therapy enhances immunocytokine-mediated antitumor effects and induces long-term memory. Cancer Immunol Immunother 56, 1765-1774
112Shurin, G.V. et al. (1998) Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand. Nat Immun 16(5–6), 263-274
113Gorter, A. and Meri, S. (1999) Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 20, 576-582
114Shen, W. and Ladisch, S. (2002) Ganglioside GD1a impedes lipopolysaccharide-induced maturation of human dendritic cells. Cell Immunol 220, 125-133
115Caldwell, S. et al. (2003) Mechanisms of ganglioside inhibition of APC function. J Immunol 171, 1676-1683
116Shurin, G.V. et al. (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61, 363-369
117Li, R., Villacreses, N. and Ladisch, S. (1995) Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res 55, 211-214
118Ferrone, S. and Foon, K.A. (2001) Tumor associated antigens (TAA) mimicry and immunotherapy of malignant diseases: from anti-idiotypic antibodies to peptide mimics. Cancer Chemother Biol Response Modif 19, 309-326
119Cheung, N.K. et al. (2000) Induction of Ab3 and Ab3′ antibody is associated with longterm survival after anti-GD2 antibody therapy of stage 4 neuroblastoma. Clin Cancer Res 6, 2653-2660
120Luo, W. et al. (2006) Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects. J Immunol 176, 6046-6054
121Fest, S. et al. (2006) Characterization of GD2 peptide mimotope DNA vaccines effective against spontaneous neuroblastoma metastases. Cancer Res 66, 10567-10575
122Coughlin, C.M. et al. (2004) RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy. Blood 103, 20462054
123Rossig, C. and Brenner, M.K. (2004) Genetic modification of T lymphocytes for adoptive immunotherapy. Mol Ther 10, 5-18
124Rossig, C. et al. (2001) Targeting of GD2-positive tumor cells by human T lymphoctyes engineered to express chimeric T-cell receptor genes. Int J Cancer 94, 228-236
125Gonzalez, S. et al. (2004) Genetic engineering of cytotoxic T lymphocytes for adoptive T-cell therapy of neuroblastoma. J Gene Med 6, 704-711
126Park, J.R. et al. (2007) Adoptive transfer of chimeric antigen receptor re-directed cytotoxic T lymphocyte clones in patients with neuroblastoma. Mol Ther 15, 825-833
127Jensen, M.C. et al. (2000) Human T lymphocyte genetic modification with naked DNA. Mol Ther 1, 49-55
128Serrano, L.M. et al. (2006) Differentiation of naïve cord-blood T cells into CD19-specific cytolytic effectors for post-transplantation adoptive immunotherapy. Blood 107, 2643-2652
129Cooper, L.J. et al. (2006) Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma. Cytotherapy 8, 105-117
130Savoldo, B. et al. (2007) Epstein Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30δ artificial chimeric T-cell receptor for immunotherapy of Hodgkins disease. Blood 110, 2620-2630
131Pule, M.A. et al. (2005) A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther 12, 933-941
132Ferrarini, M. et al. (2002) Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol 23, 14-28
133Laky, K. et al. (1998) The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells. J Immunol 161, 707-713
134Otto, M. et al. (2005) Combination immunotherapy with clinical-scale enriched human γδ T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma. Clin Cancer Res 11, 8486-8491
135Whittington, H.A., Hancock, J. and Kemshead, J.T. (2001) Generation of humanized single chain Fv (Scfv) derived from the monoclonal ERIC-1 recognizing the human neural cell adhesion molecule. Med Pediatr Oncol 36, 243-246
136Cheung, N.K. et al. (2004) Single chain Fv-streptavidin substantially improved therapeutic index in multistep targeting directed at disialoganglioside GD2. J Nucl Med 45, 867-877
137Occhino, M. et al. (2004) Generation and characterization of dimeric small immunoproteins specific for neuroblastoma associated antigen GD2. Int J Mol Med 14, 383-388
138Roque-Navarro, L. et al. (2003) Humanization of predicted T-cell epitopes reduces the immunogenicity of chimeric antibodies: new evidence supporting a simple method. Hybrid Hybridomics 4, 245-257
139Siberil, S. et al. (2007) FcγR: The key to optimize therapeutic antibodies? Crit Rev Oncol Hematol 62, 26-33

The Children's Oncology Group site provides general information for patients, families and providers in the field of paediatric oncology. There are links to information specific for neuroblastoma as well as information about ongoing clinical trials in neuroblastoma:

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