Disialoganglioside GD2 as a therapeutic target for human diseases

Expert Opinion on Therapeutic Targets

Volumn 19, Issue 3, 2015, Pages 349-362

  Suzuki, Maya ^a   Cheung, Nai Kong V ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Cancer; GD2; Immunotherapy; MAb

Indexed keywords

ANTINEOPLASTIC AGENT; BISPECIFIC ANTIBODY; CHIMERIC ANTIBODY; CHIMERIC ANTIGEN RECEPTOR; GANGLIOSIDE GD2; GANGLIOSIDE GD2 MONOCLONAL ANTIBODY; GANGLIOSIDE GD2 VACCINE; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; VACCINE; GANGLIOSIDE; GANGLIOSIDE, GD2;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; BIOCHEMISTRY; BREAST CANCER; CANCER DIAGNOSIS; CANCER GROWTH; CANCER RESISTANCE; CANCER THERAPY; CARCINOGENESIS; CELL COMMUNICATION; CELL RENEWAL; COMPLEMENT ACTIVATION; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG SELECTIVITY; EMBRYO DEVELOPMENT; EX VIVO STUDY; GENETIC ENGINEERING; HUMAN; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; MELANOMA; METASTASIS; NATURAL KILLER CELL; NEOPLASM; NEUROBLASTOMA CELL; NONHUMAN; PHAGOCYTOSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHYSIOLOGY; POINT MUTATION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; VERTEBRATE; ADULT; ANIMAL; CHILD; DRUG DESIGN; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY;

ADULT; ANIMALS; ANTINEOPLASTIC AGENTS; CHILD; DRUG DESIGN; GANGLIOSIDES; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS;

EID: 84923090047     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2014.986459     Document Type: Review

References (133)

1. Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010;363:1324-34
2. Cheung NK, Cheung IY, Kushner BH, et al. Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. J Clin Oncol 2012;30:3264-70
3. Kramer K, Humm JL, Souweidane MM, et al. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol 2007;25:5465-70
4. Louis CU, Savoldo B, Dotti G, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 2011;118:6050-6
5. Manzke O, Russello O, Leenen C, et al. Immunotherapeutic strategies in neuroblastoma: antitumoral activity of deglycosylated Ricin A conjugated anti-GD2 antibodies and anti-CD3xanti-GD2 bispecific antibodies. Med Pediatr Oncol 2001;36:185-9
6. Yankelevich M, Kondadasula SV, Thakur A, et al. Anti-CD3 x anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets. Pediatr Blood Cancer 2012;59(7):1198-205
7. Ahmed M, Cheung NK. Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. FEBS Lett 2014;588:288-97
8. Jin HJ, Nam HY, Bae YK, et al. GD2 expression is closely associated with neuronal differentiation of human umbilical cord blood-derived mesenchymal stem cells. Cell Mol Life Sci 2010;67:1845-58
9. Kailayangiri S, Altvater B, Meltzer J, et al. The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting. Br J Cancer 2012;106:1123-33
10. Martinez C, Hofmann TJ, Marino R, et al. Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 2007;109:4245-8
11. Mennel HD, Bosslet K, Wiegandt H, et al. Expression of GD2-epitopes in human intracranial tumors and normal brain. Exp Toxicol Pathol 1992;44:317-24
12. Yanagisawa M, Yoshimura S, Yu RK. Expression of GD2 and GD3 gangliosides in human embryonic neural stem cells. ASN Neuro 2011;3:e00054
13. Battula VL, Shi Y, Evans KW, et al. Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis. J Clin Invest 2012;122:2066-78
14. Liang YJ, Ding Y, Levery SB, et al. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells. Proc Natl Acad Sci USA 2013;110:4968-73
15. Lammie G, Cheung N, Gerald W, et al. Ganglioside gd(2) expression in the human nervous-system and in neuroblastomas-an immunohistochemical study. Int J Oncol 1993;3:909-15
16. Cheung NK, Neely JE, Landmeier B, et al. Targeting of ganglioside GD2 monoclonal antibody to neuroblastoma. J Nucl Med 1987;28:1577-83
17. Tsuchida T, Saxton RE, Morton DL, et al. Gangliosides of human melanoma. Cancer 1989;63:1166-74
18. Cheresh DA, Pierschbacher MD, Herzig MA, et al. Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. J Cell Biol 1986;102:688-96
19. Chang HR, Cordon-Cardo C, Houghton AN, et al. Expression of disialogangliosides GD2 and GD3 on human soft tissue sarcomas. Cancer 1992;70:633-8
20. Modak S, Gerald W, Cheung NK. Disialoganglioside GD2 and a novel tumor antigen: potential targets for immunotherapy of desmoplastic small round cell tumor. Med Pediatr Oncol 2002;39:547-51
21. Wu ZL, Schwartz E, Seeger R, et al. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res 1986;46:440-3
22. Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 2009;15:5323-37
23. Dobrenkov K, Cheung NKV. GD2-targeted immunotherapy and radioimmunotherapy. Seminars in oncology 2014;41:589-612
24. Klenk E. Uber die Ganglioside, eine neue Gruppe von zuckerhaltigen Gehirnlipoiden. Hoppe-Seyler's Zeitschrift für Physiologische Chemie 1942;273:76-86
25. Svennerholm L. Ganglioside designation. Adv Exp Med Biol 1980;125:11
26. Julien S, Bobowski M, Steenackers A, et al. How do gangliosides regulate RTKs signaling? Cells 2013;2:751-67
27. Furukawa K, Takamiya K, Furukawa K. Beta1, 4-N-acetylgalactosaminyltransferase-GM2/GD2 synthase: a key enzyme to control the synthesis of brain-enriched complex gangliosides. Biochim Biophys Acta 2002;1573:356-62
28. Cheung NK, Cheung IY, Kramer K, et al. Key role for myeloid cells: phase II results of anti-GD2 antibody 3F8 plus granulocyte-macrophage colony-stimulating factor for chemoresistant osteomedullary neuroblastoma. Int J Cancer 2014;135:2199-205
29. Hu J, Huang X, Ling CC, et al. Reducing epitope spread during affinity maturation of an anti-ganglioside GD2 antibody. J Immunol 2009;183:5748-55
30. Ye JN, Cheung NK. A novel O-acetylated ganglioside detected by anti-GD2 monoclonal antibodies. Int J Cancer 1992;50:197-201
31. Alvarez-Rueda N, Desselle A, Cochonneau D, et al. A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity. PLoS One 2011;6:e25220
32. Suzuki K. The pattern of mammalian brain gangliosides. II. Evaluation of the extraction procedures, postmortem changes and the effect of formalin preservation. J Neurochem 1965;12:629-38
33. Avrova NF. Brain ganglioside patterns of vertebrates. J Neurochem 1971;18:667-74
34. Saxena S, Wahl J, Huber-Lang MS, et al. Generation of murine sympathoadrenergic progenitor-like cells from embryonic stem cells and postnatal adrenal glands. PLoS One 2013;8:e64454
35. Svennerholm L, Bostrom K, Fredman P, et al. Human brain gangliosides: developmental changes from early fetal stage to advanced age. Biochim Biophys Acta 1989;1005:109-17
36. Rutishauser U. Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nat Rev Neurosci 2008;9:26-35
37. Ohmi Y, Ohkawa Y, Yamauchi Y, et al. Essential roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues. Neurochem Res 2012;37:1185-91
38. Xu J, Liao W, Gu D, et al. Neural ganglioside GD2 identifies a subpopulation of mesenchymal stem cells in umbilical cord. Cell Physiol Biochem 2009;23:415-24
39. Yamashiro S, Ruan S, Furukawa K, et al. Genetic and enzymatic basis for differential expression of GM2 and GD2 gangliosides in human cancer cell lines. Cancer Res 1993;53:5395-400
40. Furukawa K, Hamamura K, Ohkawa Y, et al. Disialyl gangliosides enhance tumor phenotypes with differential modalities. Glycoconj J 2012;29:579-84
41. Shibuya H, Hamamura K, Hotta H, et al. Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3. Cancer Sci 2012;103:1656-64
42. Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol 2000;2:E231-6
43. Probstmeier R, Pesheva P. Tenascin-c inhibits B1 integrin-dependent cell adhesion and neurite outgrowth on fibronectin by a disialoganglioside-mediated signaling mechanism. Glycobiology 1999;9:101-14
44. Wu L, Bernard-Trifilo JA, Lim Y, et al. Distinct FAK-Src activation events promote alpha5beta1 and alpha4beta1 integrin-stimulated neuroblastoma cell motility. Oncogene 2008;27:1439-48
45. Dong L, Liu Y, Colberg-Poley AM, et al. Induction of GM1a/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function. Glycoconj J 2011;28:137-47
46. Hettmer S, Malott C, Woods W, et al. Biological stratification of human neuroblastoma by complex "B" pathway ganglioside expression. Cancer Res 2003;63:7270-6
47. Hettmer S, McCarter R, Ladisch S, et al. Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid. Br J Cancer 2004;91:389-97
48. Shurin GV, Shurin MR, Bykovskaia S, et al. Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 2001;61:363-9
49. Shurin GV, Gerein V, Lotze MT, et al. Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand. Nat Immun 1998;16:263-74
50. Biswas S, Biswas K, Richmond A, et al. Elevated levels of select gangliosides in T cells from renal cell carcinoma patients is associated with T cell dysfunction. J Immunol 2009;183:5050-8
51. Lee HC, Wondimu A, Liu Y, et al. Ganglioside inhibition of CD8+ T cell cytotoxicity: interference with lytic granule trafficking and exocytosis. J Immunol 2012;189:3521-7
52. Wondimu A, Liu Y, Su Y, et al. Gangliosides drive the tumor infiltration and function of myeloid-derived suppressor cells. Cancer Res 2014;74:5449-57
53. Jales A, Falahati R, Mari E, et al. Ganglioside-exposed dendritic cells inhibit T-cell effector function by promoting regulatory cell activity. Immunology 2011;132:134-43
54. Schulz G, Cheresh DA, Varki NM, et al. Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 1984;44:5914-20
55. Czaplicki D, Horwacik I, Kowalczyk A, et al. New method for quantitative analysis of GD2 ganglioside in plasma of neuroblastoma patients. Acta Biochim Pol 2009;56:423-31
56. Cheung NK, Saarinen UM, Neely JE, et al. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res 1985;45:2642-9
57. Thurin J, Thurin M, Kimoto Y, et al. Monoclonal antibody-defined correlations in melanoma between levels of GD2 and GD3 antigens and antibody-mediated cytotoxicity. Cancer Res 1987;47:1229-33
58. Mujoo K, Cheresh DA, Yang HM, et al. Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth. Cancer Res 1987;47:1098-104
59. Pichla SL, Murali R, Burnett RM. The crystal structure of a Fab fragment to the melanoma-associated GD2 ganglioside. J Struct Biol 1997;119:6-16
60. Ahmed M, Goldgur Y, Hu J, et al. In silico driven redesign of a clinically relevant antibody for the treatment of GD2 positive tumors. PLoS One 2013;8:e63359
61. Yao L, Li K, Peng W, et al. An aberrant spliced transcript of focal adhesion kinase is exclusively expressed in human breast cancer. J Transl Med 2014;12:136
62. Aixinjueluo W, Furukawa K, Zhang Q, et al. Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: roles of anoikis. J Biol Chem 2005;280:29828-36
63. Yoshida S, Kawaguchi H, Sato S, et al. An anti-GD2 monoclonal antibody enhances apoptotic effects of anti-cancer drugs against small cell lung cancer cells via JNK (c-Jun terminal kinase) activation. Jpn J Cancer Res 2002;93:816-24
64. Liu B, Wu Y, Zhou Y, et al. Endothelin A receptor antagonism enhances inhibitory effects of anti-ganglioside GD2 monoclonal antibody on invasiveness and viability of human osteosarcoma cells. PLoS One 2014;9:e93576
65. Cheung NK, Dyer MA. Neuroblastoma: developmental biology, cancer genomics, and immunotherapy. Nat Rev Cancer 2013;13:397-411
66. Munn DH, Cheung NK. Antibody-dependent antitumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumor cytotoxicity not detected by isotope release assays. J Exp Med 1989;170:511-26
67. Munn DH, Cheung NK. Phagocytosis of tumor cells by human monocytes cultured in recombinant macrophage colony-stimulating factor. J Exp Med 1990;172:231-7
68. Cheung NK, Lazarus H, Miraldi FD, et al. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 1987;5:1430-40
69. Pearson AD, Pinkerton CR, Lewis IJ, et al. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol 2008;9:247-56
70. Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol 2009;27:1007-13.
71. Errata J Clin Oncol 2014;32:1862-3
72. Cheung IY, Hsu K, Cheung NK. Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor. J Clin Oncol 2012;30:426-32
73. Tarek N, Le Luduec JB, Gallagher MM, et al. Unlicensed NK cells target neuroblastoma following anti-GD2 antibody treatment. J Clin Invest 2012;122:3260-70
74. Delgado DC, Hank JA, Kolesar J, et al. Genotypes of NK cell KIR receptors, their ligands, and Fcgamma receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res 2010;70:9554-61
75. Cheung NK, Guo H, Hu J, et al. Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo. Oncoimmunology 2012;1:477-86
76. Barker E, Mueller BM, Handgretinger R, et al. Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 1991;51:144-9
77. Mueller BM, Romerdahl CA, Gillies SD, et al. Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody. J Immunol 1990;144:1382-6
78. Terme M, Dorvillius M, Cochonneau D, et al. Chimeric antibody c.8B6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia. PLoS One 2014;9:e87210
79. Simon T, Hero B, Faldum A, et al. Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol 2004;22:3549-57
80. Simon T, Hero B, Faldum A, et al. Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy. BMC Cancer 2011;11:21
81. Yu AL, Gilman AL, Ozkaynak MF, et al. Update of outcome for high-risk neuroblastoma treated on a randomized trial of chimeric anti-GD2 antibody (ch14.18) + GM-CSF/IL2 immunotherapy in 1st response: a children's oncology group study. Adv Neuroblastoma Res; Cologne; 2014;PL013 p.67
82. Isaacs JD, Greenwood J, Waldmann H. Therapy with monoclonal antibodies. II. The contribution of Fc gamma receptor binding and the influence of C(H)1 and C(H)3 domains on in vivo effector function. J Immunol 1998;161:3862-9
83. Navid F, Sondel PM, Barfield R, et al. Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J Clin Oncol 2014;32:1445-52
84. Lode HN, Schmidt M, Seidel D, et al. Vaccination with anti-idiotype antibody ganglidiomab mediates a GD(2)-specific anti-neuroblastoma immune response. Cancer Immunol Immunother 2013;62:999-1010
85. Shusterman S, London WB, Gillies SD, et al. Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children's Oncology Group (COG) phase II study. J Clin Oncol 2010;28:4969-75
86. Albertini MR, Hank JA, Gadbaw B, et al. Phase II trial of hu14.18-IL2 for patients with metastatic melanoma. Cancer Immunol Immunother 2012;61:2261-71
87. Hank JA, Gan J, Ryu H, et al. Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma. Clin Cancer Res 2009;15:5923-30
88. Vincent M, Bessard A, Cochonneau D, et al. Tumor targeting of the IL-15 superagonist RLI by an anti-GD2 antibody strongly enhances its antitumor potency. Int J Cancer 2013;133:757-65
89. Zhao XJ. GD2 oligosaacharide: target for cytotoxic T-lymphocyte (CTL). Cancer Res 1995;182:67-74
90. Cheung NK, Modak S, Lin Y, et al. Single-chain Fv-streptavidin substantially improved therapeutic index in multistep targeting directed at disialoganglioside GD2. J Nucl Med 2004;45:867-77
91. Cheng M, Ahmed M, Xu H, et al. Structural design of disialoganglioside GD2 and CD3-bispecific antibodies to redirect T cells for tumor therapy. Int J Cancer 2015;136:476-86
92. Xu H, Cheng M, Guo HF, et al. Hu3F8 bispecific antibody to engage T CELLS against neuroblastoma. Adv Neuroblastoma Res; Cologne 2014: A-0074 p.199
93. Choi BD, Gedeon PC, Sanchez-Perez L, et al. Regulatory T cells are redirected to kill glioblastoma by an EGFRvIII-targeted bispecific antibody. Oncoimmunology 2013;2:e26757
94. Cheal SM, Xu H, Guo HF, et al. Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using an IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex. Mol Cancer Ther 2014;13:1803-12
95. Pule MA, Savoldo B, Myers GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008;14:1264-70
96. Yokoyama WM, Plougastel BF. Immune functions encoded by the natural killer gene complex. Nat Rev Immunol 2003;3:304-16
97. Li L, Liu LN, Feller S, et al. Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method. Cancer Gene Ther 2010;17:147-54
98. Esser R, Muller T, Stefes D, et al. NK cells engineered to express a GD2-specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin. J Cell Mol Med 2012;16:569-81
99. Reuland P, Geiger L, Thelen MH, et al. 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 2001;23:437-42
100. Modak S, Cheung NK. Antibody-based targeted radiation to pediatric tumors. J Nucl Med 2005;46:157S-63S
101. Kramer K, Kushner BH, Modak S, et al. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma. J Neurooncol 2010;97:409-18
102. Tong W, Gagnon M, Sprules T, et al. Small-molecule ligands of GD2 ganglioside, designed from NMR studies, exhibit induced-fit binding and bioactivity. Chem Biol 2010;17:183-94
103. Brown BS, Patanam T, Mobli K, et al. Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies. Cancer Biol Ther 2014;15:851-61
104. Pastorino F, Brignole C, Marimpietri D, et al. Doxorubicin-loaded Fab' fragments of anti-disialoganglioside immunoliposomes selectively inhibit the growth and dissemination of human neuroblastoma in nude mice. Cancer Res 2003;63:86-92
105. Tivnan A, Orr WS, Gubala V, et al. Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One 2012;7:e38129
106. Pang P, Wu C, Shen M, et al. An MRI-visible non-viral vector bearing GD2 single chain antibody for targeted gene delivery to human bone marrow mesenchymal stem cells. PLoS One 2013;8:e76612
107. Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 2011;109:923-40
108. Sordi V, Melzi R, Mercalli A, et al. Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function. Stem Cells 2010;28:140-51
109. Dai LJ, Li HY, Guan LX, et al. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res 2009;2:16-25
110. Hoon DS, Banez M, Okun E, et al. Modulation of human melanoma cells by interleukin-4 and in combination with gamma-interferon or alpha-tumor necrosis factor. Cancer Res 1991;51:2002-8
111. Shibina A, Seidel D, Somanchi SS, et al. Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity. J Mol Med (Berl) 2013;91:459-72
112. Zhang H, Zhang S, Cheung NK, et al. Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases. Cancer Res 1998;58:2844-9
113. Kim SK, Wu X, Ragupathi G, et al. Impact of minimal tumor burden on antibody response to vaccination. Cancer Immunol Immunother 2011;60:621-7
114. Ragupathi G, Livingston PO, Hood C, et al. Consistent antibody response against ganglioside GD2 induced in patients with melanoma by a GD2 lactone-keyhole limpet hemocyanin conjugate vaccine plus immunological adjuvant QS-21. Clin Cancer Res 2003;9:5214-20
115. Kushner BH, Cheung IY, Modak S, et al. Phase I trial of a bivalent gangliosides vaccine in combination with beta-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res 2014;20:1375-82
116. Bleeke M, Fest S, Huebener N, et al. Systematic amino acid substitutions improved efficiency of GD2-peptide mimotope vaccination against neuroblastoma. Eur J Cancer 2009;45:2915-21
117. Cheung NK, Canete A, Cheung IY, et al. Disialoganglioside GD2 anti-idiotypic monoclonal antibodies. Int J Cancer 1993;54:499-505
118. Sen G, Chakraborty M, Foon K, et al. Preclinical evaluation in nonhuman primates of murine monoclonal anti-idiotype antibody that mimics the disialoganglioside GD2. Clin Cancer Res 1997;3:1969-76
119. Cheung NK, Guo HF, Heller G, et al. 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 2000;6:2653-60
120. Uttenreuther-Fischer MM, Kruger JA, Fischer P. Molecular characterization of the anti-idiotypic immune response of a relapse-free neuroblastoma patient following antibody therapy: a possible vaccine against tumors of neuroectodermal origin? J Immunol 2006;176:7775-86
121. Foon K, Sen G, Hutchins L, et al. Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. Clin Cancer Res 1998;4:1117-24
122. Foon KA, Lutzky J, Baral RN, et al. Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. J Clin Oncol 2000;18:376-84
123. Zeytin HE, Tripathi PK, Bhattacharya-Chatterjee M, et al. 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 Ther 2000;7:1426-36
124. Bolesta E, Kowalczyk A, Wierzbicki A, et al. DNA vaccine expressing the mimotope of GD2 ganglioside induces protective GD2 cross-reactive antibody responses. Cancer Res 2005;65:3410-18
125. Fest S, Huebener N, Weixler S, et al. Characterization of GD2 peptide mimotope DNA vaccines effective against spontaneous neuroblastoma metastases. Cancer Res 2006;66:10567-75
126. Regina Todeschini A, Hakomori SI. Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta 2008;1780:421-33
127. Helfand SC, Hank JA, Gan J, et al. Lysis of human tumor cell lines by canine complement plus monoclonal antiganglioside antibodies or natural canine xenoantibodies. Cell Immunol 1996;167:99-107
128. Soergel SA, MacEwen EG, Vail DM, et al. The immunotherapeutic potential of activated canine alveolar macrophages and antitumor monoclonal antibodies in metastatic canine melanoma. J Immunother 1999;22:443-53
129. Huang Q, Zhou X, Liu D, et al. A new liquid chromatography/tandem mass spectrometry method for quantification of gangliosides in human plasma. Anal Biochem 2014;455:26-34
130. Ahmed M, Hu J, Cheung NK. Structure based refinement of a humanized monoclonal antibody that targets tumor antigen disialoganglioside GD2. Front Immunol 2014;5:372
131. Kramer K, Pandit-Taskar N, Zanzonico P, et al. High risk and recurrent medulloblastoma (MB): lessons learned using radioimmunotherapy. International Symposium of Pediatric Neuro-Oncology; Singapore; 2014
132. Kramer K, Kushner B, Modak S, et al. Recurrent neuroblastoma metastatic to the central nervous system: is it curable? Adv Neuroblastoma Res; Cologne 2014: A-0241 p.138
133. Kushner BH, Kramer K, Modak S, et al. Successful multifold dose escalation of anti-GD2 monoclonal antibody 3F8 in patients with neuroblastoma: a phase I study. J Clin Oncol 2011;29:1168-74