Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-30T19:05:03.127Z Has data issue: false hasContentIssue false
  • English
  • Français

Antibody-based immunotherapy in high-risk neuroblastoma

Published online by Cambridge University Press:  17 December 2007

Erik Johnson ,
Shannon M. Dean  and
Paul M. Sondel
Erik Johnson
Affiliation:
Department of Surgery, The University of Wisconsin-Madison, WI 53792, USA.
Shannon M. Dean
Affiliation:
Department of Pediatrics, The University of Wisconsin-Madison, WI 53792, USA.
Paul M. Sondel*
Affiliation:
Departments of Pediatrics, Human Oncology and Genetics, andUniversity of Wisconsin Paul P. Carbone Cancer Center, The University of Wisconsin-Madison, WI 53792, USA.
*
*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: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

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.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 34 , December 2007 , pp. 1 - 21
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Cheung, N.K., Kushner, B.H. and Kramer, K. (2001) Monoclonal antibody-based therapy of neuroblastoma. Hematol Oncol Clin North Am 15, 853-866CrossRefGoogle ScholarPubMed
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 WilkinsGoogle Scholar
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, SaundersGoogle Scholar
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 18,1260-1268CrossRefGoogle ScholarPubMed
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, 2607-2613CrossRefGoogle ScholarPubMed
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 341,1165-1173CrossRefGoogle ScholarPubMed
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, 649-658CrossRefGoogle Scholar
8Franks, L.M. et al. (1997) Neuroblastoma in adults and adolescents: An indolent course with poor survival. Cancer 79, 2028-20353.0.CO;2-V>CrossRefGoogle ScholarPubMed
9Sondel, P.M. and Hank, J.A. (2001) Antibody-directed, effector cell-mediated tumor destruction. Hematol Oncol Clin North Am 15, 703-721CrossRefGoogle ScholarPubMed
10Stephenson, J. (1995) Reengineered mononclonal antibodies step up to the plate in cancer studies. JAMA 274, 1821-1822CrossRefGoogle Scholar
11Sondel, P.M. et al. (2003) Preclinical and clinical development of immunocytokines. Curr Opin Investig Drugs 4, 696-700Google ScholarPubMed
12Jurcic, J.G., Scheinberg, D.A. and Houghton, A.N. (1997) Monoclonal antibody therapy of cancer. Cancer Chemother Biol Resp Mod 17, 195-216Google ScholarPubMed
13Moss, T.J. et al. (1991) Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma. N Engl J Med 324, 219-226CrossRefGoogle ScholarPubMed
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, 4067-4076CrossRefGoogle ScholarPubMed
15Colucci, F., Caligiuri, M.A. and Santo, J.P. (2003) What does it take to make a natural killer cell? Nat Rev Immunol 3, 413-425CrossRefGoogle Scholar
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 PressCrossRefGoogle Scholar
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, 1430-1440CrossRefGoogle ScholarPubMed
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, 1098-1104Google ScholarPubMed
19Svennerholm, L. et al. (1994) Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord. Biochem Biophys Acta 1214, 115-123CrossRefGoogle ScholarPubMed
20Schulz, G. et al. (1984) Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma. Cancer Res 44, 5914-5920Google ScholarPubMed
21Nadler, L.M. et al. (1981) Diagnosis and treatment of human leukemias and lymphomas utilizing monoclonal antibodies. Prog Hematol 12,187-225Google ScholarPubMed
22Kramer, K. et al. (1998) Disialoganglioside GD2 loss following monoclonal antibody therapy is rare in neuroblastoma. Clin Cancer Res 4, 2135-2139Google ScholarPubMed
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, 515-519CrossRefGoogle Scholar
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, 1217-1223Google Scholar
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 PressGoogle Scholar
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, 769-776Google ScholarPubMed
27Cheung, N.K. et al. (1998) 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study. Int J Oncol 12, 1299-1306Google ScholarPubMed
28Cheung, N.K. (2000) Monoclonal antibody-based therapy for neuroblastoma. Curr Oncol Rep 2(6), 547-553CrossRefGoogle ScholarPubMed
29Cheung, I.Y. et al. (2003) Early molecular response in marrow is highly prognostic following treatment with anti-GD2 and GM-CSF. JCO 21, 3853-3858CrossRefGoogle Scholar
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, 1087-1093CrossRefGoogle Scholar
31Lammie, G.A. et al. (1993) Ganglioside GD2 expression in the human nervous system and in neuroblastomas: an immunohistochemical study. Int J Oncol 3, 909-915Google Scholar
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, 145-151CrossRefGoogle ScholarPubMed
33Yuki, N. et al. (1997) Pathogenesis of the neurotoxicity caused by anti-GD antibody therapy. J Neurol Sci 149, 127-130CrossRefGoogle Scholar
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, 4189-4194CrossRefGoogle Scholar
35Cheung, N.K. et al. (1988) Decay-accelerating factor protects human tumor cells from compelement-mediated cytotoxicity in vitro. J Clin Invest 81, 1122-1128CrossRefGoogle ScholarPubMed
36Kushner, B.H. and Cheung, N.K. (1989) GM-CSF enhances 3F8 monoclonal antibody-dependent cellular cytotoxicity against human melanoma and neuroblastoma. Blood 73, 1936–1941CrossRefGoogle ScholarPubMed
37Chen, S. et al. (2000) Surface antigen expression and complement susceptibility of differentiated neuroblastoma clones. Am J Pathol 156, 1085-1091CrossRefGoogle ScholarPubMed
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, 2857-2861Google ScholarPubMed
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, 5969Google ScholarPubMed
40Munn, D.H. and Cheung, N.K. (1987) Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity against human melanoma. Cancer Res 47, 6600-6605Google ScholarPubMed
41Barker, E. et al. (1991) Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Research 51, 144-149Google ScholarPubMed
42Handgretinger, R. et al. (1992) A Phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother 35, 199-204CrossRefGoogle ScholarPubMed
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, 184-193CrossRefGoogle Scholar
44Saleh, M.N. et al. (1992) Phase I trial of the murine monoclonal anti-GD antibody 14.G2a in metastatic melanoma. Cancer Res 52, 4342-4347Google Scholar
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, 261-267CrossRefGoogle ScholarPubMed
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, 2169-2180CrossRefGoogle ScholarPubMed
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, 331-338CrossRefGoogle Scholar
48Hank, J.A. et al. (1990) Augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin-2. Cancer Res 50, 5234-5239Google ScholarPubMed
49Barker, E. et al. (1991) Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 51, 144-149Google ScholarPubMed
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, 1022-1028CrossRefGoogle ScholarPubMed
51Baldwin, G.C. et al. (1993) Colony stimulating factor enhancement of myeloid effector cell cytotoxicity towards neuroectodermal tumor cells. Br J Haematol 83, 545-553CrossRefGoogle Scholar
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, 4166-4173CrossRefGoogle ScholarPubMed
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, 4077-4085CrossRefGoogle ScholarPubMed
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, 317-3333.0.CO;2-W>CrossRefGoogle ScholarPubMed
55Sondel, P.M. et al. (1986) Destruction of autologous human lymphocytes by IL2 activated cytotoxic cells. J Immunol 137, 502-511CrossRefGoogle Scholar
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, 285-295CrossRefGoogle ScholarPubMed
57Sondel, P.M. and Hank, J.A. (1997) Combination therapy with interleukin-2 and antitumor monoclonal antibodies. Cancer J Sci Am 3, S121-127Google ScholarPubMed
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 ScienceGoogle Scholar
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, 29-37CrossRefGoogle ScholarPubMed
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, 2281-2290CrossRefGoogle ScholarPubMed
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, 599-605CrossRefGoogle ScholarPubMed
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, 1755-1758Google ScholarPubMed
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, 50-61CrossRefGoogle ScholarPubMed
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, 3388-3393CrossRefGoogle ScholarPubMed
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, 1235-1246CrossRefGoogle ScholarPubMed
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, 797-806CrossRefGoogle Scholar
67Cheung, N.K. et al. (2002) Orally administered beta-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol Immunother 51, 557-564CrossRefGoogle ScholarPubMed
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, 185-1893.0.CO;2-J>CrossRefGoogle ScholarPubMed
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, 579-584Google ScholarPubMed
70Thomas, P.B. et al. (2002) Effective targeted cytotoxicity of neuroblastoma Cells. J Pediatr Surg 37, 539-544CrossRefGoogle ScholarPubMed
71Juhl, H. et al. (1997) Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells. Immunobiology 197, 444-459CrossRefGoogle ScholarPubMed
72Holzer, U. et al. (1995) Superantigen-staphylococcal-enterotoxin A-dependent and antibody-targeted lysis of GD2-positive neuroblastoma cells. Cancer Immunol Immunother 41, 129-136Google ScholarPubMed
73Ohta, S. et al. (1993) Cytotoxicity of adriamycin-containing immunoliposomes targeted with anti-ganglioside monoclonal antibodies. Anticancer Res 13, 331-336Google ScholarPubMed
74Raffaghello, L. et al. (2003) In vitro and in vivo antitumor activity of liposomal fenretinide targeted to human neuroblastoma. Int J Cancer 104, 559-567CrossRefGoogle ScholarPubMed
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, 437-444CrossRefGoogle Scholar
76Goldman, A. et al. (1984) Immunolocalization of neuroblastoma using radiolabeled monoclonal antibody UJ13A. J Pediatr 105, 252-256CrossRefGoogle ScholarPubMed
77Berthold, F. et al. (1990) Immunoscintigraphic imaging of mIBG-negative metastases in neuroblastoma. Am J Pediatr Hematol Oncol 12, 61-62CrossRefGoogle ScholarPubMed
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, 539-546CrossRefGoogle ScholarPubMed
79Modak, S. and Cheung, N.K. (2005) Antibody based targeted radiation to pediatric tumors. J Nucl Med 46, 157S-163SGoogle ScholarPubMed
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, 227-2303.0.CO;2-U>CrossRefGoogle ScholarPubMed
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, 1510-15193.0.CO;2-I>CrossRefGoogle Scholar
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, 538-548Google Scholar
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, 114-123CrossRefGoogle ScholarPubMed
84Kramer, K. et al. (2000) Targeted radioimmunotherapy for leptomeningeal cancer using I131-3F8. Med Pediatr Oncol 35, 716-7183.0.CO;2-0>CrossRefGoogle Scholar
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, 4048-4054Google ScholarPubMed
86Lode, H.N. et al. (1998) Immunocytokines: a promising approach to cancer immunotherapy. Pharmacol Ther 80, 277-292CrossRefGoogle ScholarPubMed
87Gillies, S.D. et al. (1993) Biological activity and in vivo clearance of antitumor antibody/cytokine fusion proteins. Bioconjugate Chem 4, 230-235CrossRefGoogle ScholarPubMed
88Gan, J. et al. (1999) Specific ELISA systems for quantitation of antibody-cytokine fusion proteins. Clin Diagn Lab Immunol 6, 236-242CrossRefGoogle Scholar
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, 1428-1432CrossRefGoogle ScholarPubMed
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, 3680-3688Google ScholarPubMed
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, 1101-1114CrossRefGoogle ScholarPubMed
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, 1951-1959Google ScholarPubMed
93Lode, H.N. et al. (1997) Targeted interleukin-2 therapy of spontaneous neuroblastoma metastases to bone marrow. J Natl Cancer Inst 89, 1586-1594CrossRefGoogle ScholarPubMed
94Lode, H.N. et al. (1998) Natural killer cell mediated eradication of neuroblastoma metastases to bone marrow by targeted IL2 therapy. Blood 91, 1706-1715CrossRefGoogle Scholar
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, 1750-1759CrossRefGoogle ScholarPubMed
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, 4259-4263Google ScholarPubMed
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, 1398-1402CrossRefGoogle ScholarPubMed
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, 3549-3557CrossRefGoogle ScholarPubMed
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), 147-152CrossRefGoogle ScholarPubMed
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, 84-87CrossRefGoogle ScholarPubMed
101Heslop, H.E. et al. (1996) Use of gene marking in bone marrow transplantation. Cancer Detect Prev 20, 108-113Google ScholarPubMed
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, 141-147CrossRefGoogle ScholarPubMed
103Beaujean, F. et al. (1989) Hematopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow. Bone Marrow Transplant 4, 537-541Google ScholarPubMed
104Gulati, S. et al. (1990) Photoradiation methods for purging autologous bone marrow grafts. Prog Clin Biol Res 333, 87-102Google ScholarPubMed
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, 5083-5089Google ScholarPubMed
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, 3042-3048CrossRefGoogle ScholarPubMed
107Donovan, J. et al. (2000) CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol 35, 677-6823.0.CO;2-H>CrossRefGoogle ScholarPubMed
108Handgretinger, R. et al. (2003) Tumour cell contamination of autologous stem cell grafts in high-risk neuroblastoma: the good news? Br J Cancer 88, 1874-1877CrossRefGoogle ScholarPubMed
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, 41-52CrossRefGoogle ScholarPubMed
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, 1500-1507Google ScholarPubMed
111Neal, Z.C. et al. (2007) Flt3-L gene therapy enhances immunocytokine-mediated antitumor effects and induces long-term memory. Cancer Immunol Immunother 56, 1765-1774CrossRefGoogle ScholarPubMed
112Shurin, G.V. et al. (1998) Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand. Nat Immun 16(5–6), 263-274CrossRefGoogle Scholar
113Gorter, A. and Meri, S. (1999) Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 20, 576-582CrossRefGoogle ScholarPubMed
114Shen, W. and Ladisch, S. (2002) Ganglioside GD1a impedes lipopolysaccharide-induced maturation of human dendritic cells. Cell Immunol 220, 125-133CrossRefGoogle ScholarPubMed
115Caldwell, S. et al. (2003) Mechanisms of ganglioside inhibition of APC function. J Immunol 171, 1676-1683CrossRefGoogle ScholarPubMed
116Shurin, G.V. et al. (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61, 363-369Google ScholarPubMed
117Li, R., Villacreses, N. and Ladisch, S. (1995) Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res 55, 211-214Google ScholarPubMed
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, 309-326Google Scholar
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, 2653-2660Google Scholar
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, 6046-6054CrossRefGoogle ScholarPubMed
121Fest, S. et al. (2006) Characterization of GD2 peptide mimotope DNA vaccines effective against spontaneous neuroblastoma metastases. Cancer Res 66, 10567-10575CrossRefGoogle ScholarPubMed
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, 2046–2054CrossRefGoogle ScholarPubMed
123Rossig, C. and Brenner, M.K. (2004) Genetic modification of T lymphocytes for adoptive immunotherapy. Mol Ther 10, 5-18CrossRefGoogle ScholarPubMed
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, 228-236CrossRefGoogle Scholar
125Gonzalez, S. et al. (2004) Genetic engineering of cytotoxic T lymphocytes for adoptive T-cell therapy of neuroblastoma. J Gene Med 6, 704-711CrossRefGoogle ScholarPubMed
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, 825-833CrossRefGoogle ScholarPubMed
127Jensen, M.C. et al. (2000) Human T lymphocyte genetic modification with naked DNA. Mol Ther 1, 49-55CrossRefGoogle Scholar
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, 2643-2652CrossRefGoogle Scholar
129Cooper, L.J. et al. (2006) Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma. Cytotherapy 8, 105-117CrossRefGoogle ScholarPubMed
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, 2620-2630CrossRefGoogle Scholar
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, 933-941CrossRefGoogle ScholarPubMed
132Ferrarini, M. et al. (2002) Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol 23, 14-28CrossRefGoogle ScholarPubMed
133Laky, K. et al. (1998) The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells. J Immunol 161, 707-713CrossRefGoogle ScholarPubMed
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, 8486-8491CrossRefGoogle ScholarPubMed
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, 243-2463.0.CO;2-5>CrossRefGoogle Scholar
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, 867-877Google ScholarPubMed
137Occhino, M. et al. (2004) Generation and characterization of dimeric small immunoproteins specific for neuroblastoma associated antigen GD2. Int J Mol Med 14, 383-388Google ScholarPubMed
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, 245-257CrossRefGoogle Scholar
139Siberil, S. et al. (2007) FcγR: The key to optimize therapeutic antibodies? Crit Rev Oncol Hematol 62, 26-33CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

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:

http://www.curesearch.orgGoogle Scholar
http://www.cancer.gov/cancertopics/types/neuroblastoma/Google Scholar