Immunogenicity of dendritic-tumor fusion hybrids and their utility in cancer immunotherapy

Critical Reviews in Immunology

Volumn 27, Issue 5, 2007, Pages 463-483

  Shu, Suyu ^a   Zheng, Rongxiu ^a   Lee, Walter T ^a   Cohen, Peter A ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

Cancer immunotherapy; Clinical trials; Dendritic cells; Dendritic tumor fusion hybrids; Electrofusion; Tumor associated antigens

Indexed keywords

B7 ANTIGEN; CD14 ANTIGEN; CD4 ANTIGEN; CD40 ANTIGEN; CD8 ANTIGEN; CD86 ANTIGEN; DENDRITIC CELL VACCINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 12; INTERLEUKIN 6; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 3; TOLL LIKE RECEPTOR;

ANTIGEN PRESENTING CELL; CANCER IMMUNOTHERAPY; DENDRITE; DENDRITIC CELL; DRUG TOLERABILITY; ELECTROFUSION (CELL); HUMAN; HUMAN CELL; HYBRID CELL; IMMUNOGENICITY; IN VITRO STUDY; IN VIVO STUDY; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; METASTASIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; TUMOR REGRESSION;

EID: 38049017405     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevimmunol.v27.i5.50     Document Type: Review

References (122)

1. Ashley MP, Zbar B, Hunter JT, Rapp HJ, Sugimoto T. Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery. Cancer Res. 1980;40(11):4197-203.
2. Shevach EM. Fatal attraction: tumors beckon regulatory T cells. Nat Med. 2004;10(9):900-1.
3. Steinman RM, Hemmi H. Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol. 2006;311:17-58.
4. Osada T, Clay TM, Woo CY, Morse MA, Lyerly HK. Dendritic cell-based immunotherapy. Int Rev Immunol. 2006;25(5):377-413.
5. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10(9):909-15.
6. Schreiber H. Tumor immunology. In: Paul W, editor. Fundamental immunology. 2nd ed. New York: Raven Press; 1989. p. 923-55.
7. Ehrlich P. The collected papers of Paul Ehrlich. London: Pergamon; 1909.
8. Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957;18(6):769-78.
9. Klein G, Sjogren HO, Klein E, Hellstrom KE. Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res. 1960;20:1561-72.
10. Novellino L, Castelli C, Parmiani G. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother. 2005;54(3):187-207.
11. Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445-80.
12. Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994;76(2):275-85.
13. Mescher MF, Curtsinger JM, Agarwal P, Casey KA, Gerner M, Hammerbeck CD, Popescu F, Xiao Z. Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev. 2006;211:81-92.
14. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811.
15. Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271-96.
16. Moser M. Dendritic cells. In: Paul W, editor. Fundamental immunology. 5th ed. Philadelphia: Williams and Wilkins; 2003. p. 445-80.
17. Snijders A, Kalinski P, Hilkens CM, Kapsenberg ML. High-level IL-12 production by human dendritic cells requires two signals. Int Immunol. 1998;10(11):1593-8.
18. Paglia P, Chiodoni C, Rodolfo M, Colombo MP. Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J Exp Med. 1996;183(1):317-22.
19. Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med. 1996;184(2):465-72.
20. Nair S, Zhou F, Reddy R, Huang L, Rouse BT. Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro. J Exp Med. 1992;175(2):609-12.
21. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Cancer immunotherapy using gene-modified dendritic cells. Curr Gene Ther. 2002;2(1):57-78.
22. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol. 2003;21(12):2415-32.
23. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 1994;264(5161):961-5.
24. Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature. 1997;388(6644):787-92.
25. Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, Steinman RM, Mellman I. Transport of peptide-MHC class II complexes in developing dendritic cells. Science. 2000;288(5465):522-7.
26. Xu W, de Zoeten E, Carr-Brendel V, Cohen EP. Coexpression of immunogenic determinants by the same cellular immunogen is required for the optimum immunotherapeutic benefit in mice with melanoma. Cancer Immunol Immunother. 1998;45(5):217-24.
27. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197-216.
28. de Jong EC, Smits HH, Kapsenberg ML. Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol. 2005;26(3):289-307.
29. Mazzoni A, Segal DM. Controlling the Toll road to dendritic cell polarization. J Leukoc Biol. 2004;75(5):721-30.
30. Hayashi T, Tanaka H, Tanaka J, Wang R, Averbook BJ, Cohen PA, Shu S. Immunogenicity and therapeutic efficacy of dendritic-tumor hybrid cells generated by electrofusion. Clin Immunol. 2002;104(1):14-20.
31. Tanaka H, Shimizu K, Hayashi T, Shu S. Therapeutic immune response induced by electrofusion of dendritic and tumor cells. Cell Immunol. 2002;220(1):1-12.
32. Kjaergaard J, Shimizu K, Shu S. Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine. Cell Immunol. 2003;225(2):65-74.
33. Kuriyama H, Shimizu K, Lee W, Kjaergaard J, Parkhurst MR, Cohen PA, Shu S. Therapeutic vaccine generated by electrofusion of dendritic cells and tumour cells. Dev Biol (Basel). 2004;116:169-78.
34. Shimizu K, Kuriyama H, Kjaergaard J, Lee W, Tanaka H, Shu S. Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy. J Immunother. 2004;27(4):265-72.
35. Kjaergaard J, Wang LX, Kuriyama H, Shu S, Plautz GE. Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines. J Neurosurg. 2005;103(1):156-64.
36. Kuriyama H, Watanabe S, Kjaergaard J, Tamai H, Zheng R, Weingberg AD, Hu H-M, Cohen PA, Plautz GE, Shu S. Mechanism of third signals provided by IL-12 and OX-40R ligation in eliciting therapeutic immunity following dendritic-tumor fusion vaccination. Cell Immunol. 2006;243(1):30-40.
37. Kim BS, Liang W, Cohen EP. Tumor-specific immunity induced by somatic hybrids. I. Lack of relationship between immunogenicity and tumorigenicity of selected hybrids. J Immunol. 1979;123(2):733-8.
38. Kim BS. Tumor-specific immunity induced by somatic hybrids. II. Elicitation of enhanced immunity against the parent plasmacytoma. J Immunol. 1979;123 (2):739-44.
39. Hui KM, Kim BS. Tumor-specific immunity induced by somatic hybrids. IV. Relationship between immunogenicity and expression of surface tumor-associated antigens. Cell Immunol. 1984;87 (2):591-600.
40. Guo Y, Wu M, Chen H, Wang X, Liu G, Li G, Ma J, Sy MS. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science. 1994;263(5146):518-20.
41. Steinman RM, Dhodapkar M. Active immunization against cancer with dendritic cells: the near future. Int J Cancer. 2001;94(4):459-73.
42. Hart DN. Dendritic cells: unique leukocyte populations which control the primary immune response. Blood. 1997;90(9):3245-87.
43. Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med. 1997;3(5):558-61.
44. Hart I, Colaco C. Immunotherapy. Fusion induces tumour rejection. Nature. 1997;388(6643):626-7.
45. Gong J, Chen D, Kashiwaba M, Li Y, Chen L, Takeuchi H, Qu H, Rowse GJ, Gendler SJ, Kufe D. Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. Proc Natl Acad Sci U S A. 1998;95(11):6279-83.
46. Gong J, Apostolopoulos V, Chen D, Chen H, Koido S, Gendler SJ, McKenzie IF, Kufe D. Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendriticcarcinoma fusion cells. Immunology. 2000;101(3):316-24.
47. Koido S, Tanaka Y, Chen D, Kufe D, Gong J. The kinetics of in vivo priming of CD4 and CD8 T cells by dendritic/tumor fusion cells in MUC1-transgenic mice. J Immunol. 2002;168(5):2111-7.
48. Celluzzi CM, Falo LD Jr. Physical interaction between dendritic cells and tumor cells results in an immunogen that induces protective and therapeutic tumor rejection. J Immunol. 1998;160(7):3081-5.
49. Melcher A, Todryk S, Bateman A, Chong H, Lemoine NR, Vile RG. Adoptive transfer of immature dendritic cells with autologous or allogeneic tumor cells generates systemic antitumor immunity. Cancer Res. 1999;59(12):2802-5.
50. Candido KA, Shimizu K, McLaughlin JC, Kunkel R, Fuller JA, Redman BG, Thomas EK, Nickoloff BJ, Mule JJ. Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents. Cancer Res. 2001;61(1):228-36.
51. Lindner M, Schirrmacher V. Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocols. Eur J Clin Invest. 2002;32(3):207-17.
52. Gong J, Koido S, Chen D, Tanaka Y, Huang L, Avigan D, Anderson K, Ohno T, Kufe D. Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood. 2002;99(7):2512-7.
53. Tanaka Y, Koido S, Ohana M, Liu C, Gong J. Induction of impaired antitumor immunity by fusion of MHC class II-deficient dendritic cells with tumor cells. J Immunol. 2005;174(3):1274-80.
54. Tanaka Y, Koido S, Xia J, Ohana M, Liu C, Cote GM, Sawyer DB, Calderwood S, Gong J. Development of antigen-specific CD8+ CTL in MHC class Ideficient mice through CD4 to CD8 conversion. J Immunol. 2004;172(12):7848-58.
55. Tanaka Y, Koido S, Chen D, Gendler SJ, Kufe D, Gong J. Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice. Clin Immunol. 2001;101 (2):192-200.
56. Akasaki Y, Kikuchi T, Homma S, Abe T, Kofe D, Ohno T. Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model. J Immunother. 2001;24(2):106-13.
57. Xia J, Tanaka Y, Koido S, Liu C, Mukherjee P, Gendler SJ, Gong J. Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/ tumor fusion cells. J Immunol. 2003;170(4):1980-6.
58. Takeda A, Homma S, Okamoto T, Kufe D, Ohno T. Immature dendritic cell/tumor cell fusions induce potent antitumour immunity. Eur J Clin Invest. 2003;33(10):897-904.
59. Chen D, Xia J, Tanaka Y, Chen H, Koido S, Wernet O, Mukherjee P, Gendler SJ, Kufe D, Gong J. Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells. Immunology. 2003;109(2):300-7.
60. Enomoto Y, Bharti A, Khaleque AA, Song B, Liu C, Apostolopoulos V, Xing PX, Calderwood SK, Gong J. Enhanced immunogenicity of heat shock protein 70 peptide complexes from dendritic cell-tumor fusion cells. J Immunol. 2006;177(9):5946-55.
61. Homma S, Kikuchi T, Ishiji N, Ochiai K, Takeyama H, Saotome H, Sagawa Y, Hara E, Kufe D, Ryan JL, Ohno T, Toda G. Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12. Eur J Clin Invest. 2005;35(4):279-86.
62. Koido S, Ohana M, Liu C, Nikrui N, Durfee J, Lerner A, Gong J. Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation. Clin Immunol. 2004;113(3):261-9.
63. Takagi Y, Kikuchi T, Niimura M, Ohno T. Antitumor effects of dendritic and tumor cell fusions are not dependent on expression of MHC class I and II by dendritic cells. Cancer Lett. 2004;213(1):49-55.
64. Lespagnard L, Mettens P, Verheyden AM, Tasiaux N, Thielemans K, van Meirvenne S, Geldhof A, De Baetselier P, Urbain J, Leo O, Moser M. Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor immunity. Int J Cancer. 1998;76(2):250-8.
65. Cao X, Zhang W, Wang J, Zhang M, Huang X, Hamada H, Chen W. Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells. Immunology. 1999;97 (4):616-25.
66. Li J, Holmes LM, Franek KJ, Burgin KE, Wagner TE, Wei Y. Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity. Cancer Immunol Immunother. 2001;50(9):456-62.
67. Liu Y, Zhang W, Chan T, Saxena A, Xiang J. Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative mature dendritic cells enhances antitumor immunity. Leuk Res. 2002;26(8):757-63.
68. McConnell EJ, Pathangey LB, Madsen CS, Gendler SJ, Mukherjee P. Dendritic cell-tumor cell fusion and staphylococcal enterotoxin B treatment in a pancreatic tumor model. J Surg Res. 2002;107(2):196-202.
69. Ogawa F, Iinuma H, Okinaga K. Dendritic cell vaccine therapy by immunization with fusion cells of interleukin-2 gene-transduced, spleen-derived dendritic cells and tumour cells. Scand J Immunol. 2004;59(5):432-9.
70. Xia D, Li F, Xiang J. Engineered fusion hybrid vaccine of IL-18 gene-modified tumor cells and dendritic cells induces enhanced antitumor immunity. Cancer Biother Radiopharm. 2004;19(3):322-30.
71. Shi M, Su L, Hao S, Guo X, Xiang J. Fusion hybrid of dendritic cells and engineered tumor cells expressing interleukin-12 induces type 1 immune responses against tumor. Tumori. 2005;91(6):531-8.
72. Du YC, Lin P, Zhang J, Lu YR, Ning QZ, Wang Q. Fusion of CpG-ODN-stimulating dendritic cells with Lewis lung cancer cells can enhance anti-tumor immune responses. Tissue Antigens. 2006;67(5):368-76.
73. Savai R, Schermuly RT, Schneider M, Pullamsetti SS, Grimminger F, Seeger W, Banat GA. Hybrid-primed lymphocytes and hybrid vaccination prevent tumor growth of lewis lung carcinoma in mice. J Immunother. 2006;29(2):175-87.
74. Simova J, Bieblova J, Jandlova T, Bubenik J. Immunotherapy of HPV 16-associated tumours with tumour cell line/dendritic cell line (TC-1/DC2.4) hybrid vaccines. Folia Biol (Praha). 2003;49(5):203-6.
75. Gong J, Avigan D, Chen D, Wu Z, Koido S, Kashiwaba M, Kufe D. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci U S A. 2000;97(6):2715-8.
76. Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D, Kufe D. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol. 2000;165(3):1705-11.
77. Soruri A, Fayyazi A, Neumann C, Schlott T, Jung T, Matthes C, Zwirner J, Riggert J, Peters JH. Ex vivo generation of human anti-melanoma autologous cytolytic T cells by dentritic cell/melanoma cell hybridomas. Cancer Immunol Immunother. 2001;50(6):307-14.
78. Sloan AE, Parajuli P. Human autologous dendritic cell-glioma fusions: feasibility and capacity to stimulate T cells with proliferative and cytolytic activity. J Neurooncol. 2003;64(1-2):177-83.
79. Lundqvist A, Palmborg A, Bidla G, Whelan M, Pandha H, Pisa P. Allogeneic tumor-dendritic cell fusion vaccines for generation of broad prostate cancer T-cell responses. Med Oncol. 2004;21(2):155-65.
80. Gong J, Koido S, Kato Y, Tanaka Y, Chen D, Jonas A, Galinsky I, DeAngelo D, Avigan D, Kufe D, Stone R. Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous myeloblasts. Leuk Res. 2004;28(12):1303-12.
81. Banat GA, Usluoglu N, Hoeck M, Ihlow K, Hoppmann S, Pralle H. Dendritic cells fused with core binding factor-beta positive acute myeloid leukaemia blast cells induce activation of cytotoxic lymphocytes. Br J Haematol. 2004;126(4):593-601.
82. Guo G, Chen S, Zhang J, Luo L, Yu J, Dong H, Xu H, Su Z, Wu L. Antitumor activity of a fusion of esophageal carcinoma cells with dendritic cells derived from cord blood. Vaccine. 2005;23(45):5225-30.
83. Koido S, Hara E, Homma S, Torii A, Toyama Y, Kawahara H, Watanabe M, Yanaga K, Fujise K, Tajiri H, Gong J, Toda G. Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells. Clin Cancer Res. 2005;11(21):7891-900.
84. Klammer M, Waterfall M, Samuel K, Turner ML, Roddie PH. Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia. Br J Haematol. 2005;129(3):340-9.
85. Koido S, Hara E, Torii A, Homma S, Toyama Y, Kawahara H, Ogawa M, Watanabe M, Yanaga K, Fujise K, Gong J, Toda G. Induction of antigen-specific CD4- and CD8-mediated T-cell responses by fusions of autologous dendritic cells and metastatic colorectal cancer cells. Int J Cancer. 2005;117 (4):587-95.
86. Vasir B, Borges V, Wu Z, Grosman D, Rosenblatt J, Irie M, Anderson K, Kufe D, Avigan D. Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation. Br J Haematol. 2005;129(5):687-700.
87. Liang W, Cohen EP. Somatic hybrid of thymus leukemia. Proc Natl Acad Sci U S A. 1975;72(5):1873-7.
88. Linardakis E, Bateman A, Phan V, Ahmed A, Gough M, Olivier K, Kennedy R, Errington F, Harrington KJ, Melcher A, Vile R. Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion. Cancer Res. 2002;62(19):5495-504.
89. Phan V, Errington F, Cheong SC, Kottke T, Gough M, Altmann S, Brandenburger A, Emery S, Strome S, Bateman A, Bonnotte B, Melcher A, Vile R. A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat Med. 2003;9(9):1215-9.
90. Neil GA, Zimmermann U. Electrofusion. Methods Enzymol. 1993;220:174-96.
91. White KL. Electrofusion of mammalian cells. Methods Mol Biol. 1995;48:283-93.
92. Stuhler G, Trefzer U, Walden P. Hybrid cell vaccination in cancer immunotherapy. Recruitment and activation of T cell help for induction of anti tumour cytotoxic T cells. Adv Exp Med Biol. 1998;451:277-82.
93. Siders WM, Vergilis KL, Johnson C, Shields J, Kaplan JM. Induction of specific antitumor immunity in the mouse with the electrofusion product of tumor cells and dendritic cells. Mol Ther. 2003;7(4):498-505.
94. Orentas RJ, Schauer D, Bin Q, Johnson BD. Electrofusion of a weakly immunogenic neuroblastoma with dendritic cells produces a tumor vaccine. Cell Immunol. 2001;213(1):4-13.
95. Yu Z, Fan Q, Hao X, Long H. Specific antitumor effects of tumor vaccine produced by electrofusion between osteosarcoma cell and dendritic cell in rats. Cell Mol Immunol. 2004;1(6):454-60.
96. Scott-Taylor TH, Pettengell R, Clarke I, Stuhler G, La Barthe MC, Walden P, Dalgleish AG. Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines. Biochim Biophys Acta. 2000;1500(3):265-79.
97. Gottfried E, Krieg R, Eichelberg C, Andreesen R, Mackensen A, Krause SW. Characterization of cells prepared by dendritic cell-tumor cell fusion. Cancer Immun. 2002;2:15-25.
98. Jantscheff P, Spagnoli G, Zajac P, Rochlitz CF. Cell fusion: an approach to generating constitutively proliferating human tumor antigen-presenting cells. Cancer Immunol Immunother. 2002;51(7):367-75.
99. Trefzer U, Walden P. Hybrid-cell vaccines for cancer immune therapy. Mol Biotechnol. 2003;25(1):63-9.
100. Goddard RV, Prentice AG, Copplestone JA, Kaminski ER. In vitro dendritic cell-induced T cell responses to B cell chronic lymphocytic leukaemia enhanced by IL-15 and dendritic cell-B-CLL electrofusion hybrids. Clin Exp Immunol. 2003;131 (1):82-9.
101. Haenssle HA, Krause SW, Emmert S, Zutt M, Kretschmer L, Schmidberger H, Andreesen R, Soruri A. Hybrid cell vaccination in metastatic melanoma: clinical and immunologic results of a phase I/II study. J Immunother. 2004;27(2):147-55.
102. Weise JB, Maune S, Gorogh T, Kabelitz D, Arnold N, Pfisterer J, Hilpert F, Heiser A. A dendritic cell based hybrid cell vaccine generated by electrofusion for immunotherapy strategies in HNSCC. Auris Nasus Larynx. 2004;31(2):149-53.
103. Weise JB, Hilpert F, Heiser A, Gorogh T, Meyer JE, Weimer J, Kruger C, Rosenau A, Wieckhorst W, Arnold N, Pfisterer J, Kabelitz D, Maune S. Electrofusion generates diverse DC-tumour cell hybrids for cancer immunotherapy. Anticancer Res. 2004;24(2B):929-34.
104. Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sharav T, Sparbier K, Sterry W, Walden P. Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results. Vaccine. 2005;23(17-18):2367-73.
105. Yu Z, Ma B, Zhou Y, Zhang M, Qiu X, Fan Q. Activation of antitumor cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous osteosarcoma. Exp Oncol. 2005;27(4):273-8.
106. Sukhorukov VL, Reuss R, Endter JM, Fehrmann S, Katsen-Globa A, Gessner P, Steinbach A, Muller KJ, Karpas A, Zimmermann U, Zimmermann H. A biophysical approach to the optimisation of dendritictumour cell electrofusion. Biochem Biophys Res Commun. 2006;346(3):829-39.
107. Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med. 2000;6(3):332-36.
108. Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, Audring H, Guo Y, Sterry W, Walden P. Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer. 2000;85(5):618-26.
109. Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, Ohno T. Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother. 2001;50(7):337-44.
110. Homma S, Matai K, Irie M, Ohno T, Kufe D, Toda G. Immunotherapy using fusions of autologous dendritic cells and tumor cells showed effective clinical response in a patient with advanced gastric carcinoma. J Gastroenterol. 2003;38(10):989-94.
111. Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sherev T, Sparbier K, Sterry W, Walden P. Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients. Int J Cancer. 2004;110(5):730-40.
112. Avigan D, Vasir B, Gong J, Borges V, Wu Z, Uhl L, Atkins M, Mier J, McDermott D, Smith T, Giallambardo N, Stone C, Schadt K, Dolgoff J, Tetreault JC, Villarroel M, Kufe D. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004;10(14):4699-708.
113. Avigan D. Dendritic cell-tumor fusion vaccines for renal cell carcinoma. Clin Cancer Res. 2004;10(18 Pt 2):6347S-52S.
114. Kikuchi T, Akasaki Y, Abe T, Fukuda T, Saotome H, Ryan JL, Kufe DW, Ohno T. Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J Immunother. 2004;27(6):452-9.
115. Homma S, Sagawa Y, Ito M, Ohno T, Toda G. Cancer immunotherapy using dendritic/tumour-fusion vaccine induces elevation of serum anti-nuclear antibody with better clinical responses. Clin Exp Immunol. 2006;144(1):41-7.
116. Misconduct claims derail German study of cancer vaccines. Nature. 2001;412:8.
117. Schiermeier Q. Cancer researcher found guilty of negligence. Nature. 2002;420(6913):258.
118. Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH. Retraction: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med. 2003;9 (9):1221.
119. Abbott A. German fraud inquiry casts a wider net of suspicion...as disillusionment reigns in task force. Nature. 2000;405(6789):871-2.
120. Shu S, Cochran AJ, Huang RR, Morton DL, Maecker HT. Immune responses in the draining lymph nodes against cancer: implications for immunotherapy. Cancer Metastasis Rev. 2006;25(2):233-42.
121. Marten A, Renoth S, Heinicke T, Albers P, Pauli A, Mey U, Caspari R, Flieger D, Hanfland P, Von Ruecker A, Eis-Hubinger AM, Muller S, Schwaner I, Lohmann U, Heylmann G, Sauerbruch T, Schmidt-Wolf IG. Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. Hum Gene Ther. 2003;14(5):483-94.
122. Parkhurst MR, DePan C, Riley JP, Rosenberg SA, Shu S. Hybrids of dendritic cells and tumor cells generated by electrofusion simultaneously present immunodominant epitopes from multiple human tumor-associated antigens in the context of MHC class I and class II molecules. J Immunol. 2003;170 (10):5317-25.