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Review Article

Dendritic cell–tumor cell hybrids and immunotherapy: what's next?

, , , , &
Pages 774-785 | Received 09 Aug 2010, Accepted 22 Dec 2010, Published online: 07 Feb 2011

References

  • Bonnotte B, Favre N, Moutet M, Fromentin A, Solary E, Martin M, . Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors. J Immunol. 1998;161:1433–8.
  • Bonnotte B, Favre N, Moutet M, Fromentin A, Solary E, Martin M, . Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes. J Immunol. 2000;164:1995–2000.
  • Nouri-Shirazi M, Banchereau J, Bell D, Burkeholder S, Kraus ET, Davoust J, . Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses. J Immunol. 2000;165:3797–803.
  • Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52.
  • Bonnotte B, Larmonier N, Favre N, Fromentin A, Moutet M, Martin M, . Identification of tumor-infiltrating macrophages as the killers of tumor cells after immunization in a rat model system. J Immunol. 2001;167:5077–83.
  • Alli R, Savithri B, Das S, Varalakshmi C, Rangaraj N, Khar A. Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: indicative of a common, innate, target-recognition paradigm? Eur J Immunol. 2004;34: 1119–26.
  • Lynch DH. The promise of 4-1BB (CD137)-mediated immunomodulation and the immunotherapy of cancer. Immunol Rev. 2008;222:277–86.
  • Croft M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol. 2009;9:271–85.
  • Watts TH. TNF/TNFR family members in costimulation of T cell responses. Ann Rev Immunol. 2005;23:23–68.
  • Couderc B, Zitvogel L, Douin-Echinard V, Djennane L, Tahara H, Favre G, . Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells. Cancer Gene Ther. 1998;5:163–75.
  • Lorenz MG, Kantor JA, Schlom J, Hodge JW. Anti-tumor immunity elicited by a recombinant vaccinia virus expressing CD70 (CD27L). Hum Gene Ther. 1999;10:1095–103.
  • Nieland JD, Graus YF, Dortmans YE, Kremers BL, Kruisbeek AM. CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response. J Immunother. 1998;21:225–36.
  • Liu X, Bai X-F, Wen J, Gao J-X, Liu J, Lu P, . B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8 + T lymphocytes in vivo. J Exp Med. 2001;194:1339–48.
  • Wallin JJ, Liang L, Bakardjiev A, Sha WC. Enhancement of CD8+ T cell responses by ICOS/B7h costimulation. J Immunol. 2001;167:132–9.
  • Cohen AD, Diab A, Perales M-A, Wolchok JD, Rizzuto G, Merghoub T, . Agonist anti-GITR antibody enhances vaccine-induced CD8+ T-cell responses and tumor immunity. Cancer Res. 2006;66:4904–12.
  • Zhou P, L'Italien L, Hodges D, Schebye XM. Pivotal roles of CD4+ effector T cells in mediating agonistic anti-GITR mAb-induced-immune activation and tumor immunity in CT26 tumors. J Immunol. 2007;179:7365–75.
  • Chaux P, Favre N, Bonnotte B, Moutet M, Martin M, Martin F. Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression. A role in the immune tolerance to antigenic tumors. Adv Exp Med Biol. 1997;417:525–8.
  • Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, . Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4: 328–32.
  • Salcedo M, Bercovici N, Taylor R, Vereecken P, Massicard S, Duriau D, . Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother. 2006;55:819–29.
  • Soleimani A, Berntsen A, Svane IM, Pedersen AE. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate. Scand J Immunol. 2009;70:481–9.
  • Bettinotti M, Panelli MC, Ruppe E, Mocellin S, Phan GQ, White DE, Marincola FM. Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA-Cw*0702-associated epitope MAGE-A12:170–178. Int J Cancer. 2003;105:210–6.
  • Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD Jr. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J Exp Med. 1996;183:283–7.
  • Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood. 2002;100:174–7.
  • Hersey P, Menzies SW, Halliday GM, Nguyen T, Farrelly ML, DeSilva C, . Phase I/II study of treatment with dendritic cell vaccines in patients with disseminated melanoma. Cancer Immunol Immunother. 2004;53:125–34.
  • Mayordomo JI, Zorina T, Storkus WJ, Zitvogel L, Celluzzi C, Falo LD, . Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med. 1995;1: 1297–302.
  • Nair SK, Hull S, Coleman D, Gilboa E, Lyerly HK, Morse MA. Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA. Int J Cancer. 1999;82:121–4.
  • Schuler-Thurner B, Dieckmann D, Keikavoussi P, Bender A, Maczek C, Jonuleit H, . Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells. J Immunol. 2000;165:3492–6.
  • Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, . Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 1999;190:1669–78.
  • Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, . Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci USA. 1995;92:8078–82.
  • Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Brocker EB, . Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol. 2006;17:563–70.
  • Slingluff CL Jr, Petroni GR, Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, . Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte–macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol. 2003;21:4016–26.
  • Mackensen A, Herbst B, Chen JL, Kohler G, Noppen C, Herr W, . Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int J Cancer. 2000;86:385–92.
  • Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate. 1996;29:371–80.
  • Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA, . Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother (1997). 2000; 23:487–98.
  • Trepiakas R, Berntsen A, Hadrup SR, Bjørn J, Geertsen PF, Straten PT, . Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. Cytotherapy. 2010;12:1–14.
  • Boczkowski D, Nair SK, Nam J-H, Lyerly HK, Gilboa E. Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells. Cancer Res. 2000;60: 1028–34.
  • 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;184:465–72.
  • Heiser A, Maurice MA, Yancey DR, Coleman DM, Dahm P, Vieweg J. Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors. Cancer Res. 2001;61:3388–93.
  • Heiser A, Maurice MA, Yancey DR, Wu NZ, Dahm P, Pruitt SK, . Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA. J Immunol. 2001;166:2953–60.
  • Kyte JA, Kvalheim G, Lislerud K, Thor Straten P, Dueland S, Aamdal S, . T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol Immunother. 2007;56:659–75.
  • Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M, . Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther. 2006;13:905–18.
  • Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, . Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res. 2003;63:2127–33.
  • Sæbøe-Larssen S, Fossberg E, Gaudernack G. mRNA-based electrotransfection of human dendritic cells and induction of cytotoxic T lymphocyte responses against the telomerase catalytic subunit (hTERT). J Immunol Methods. 2002 Jan 1;259(1–2):191–203.
  • Su Z, Dannull J, Yang BK, Dahm P, Coleman D, Yancey D, . Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol. 2005;174:3798–807.
  • Tuyaerts S, Michiels A, Corthals J, Bonehill A, Heirman C, Greef CD, . Induction of influenza matrix protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells. Cancer Gene Ther. 2003 Sep; 10(9):696–706.
  • Met Ö, Balslev E, Flyger H, Svane I. High immunogenic potential of p53 mRNA-transfected dendritic cells in patients with primary breast cancer. Breast Cancer Res Treat. 2011 Jan;125(2):395–406.
  • Ueno H, Tcherepanova I, Reygrobellet O, Laughner E, Ventura C, Palucka AK, . Dendritic cell subsets generated from CD34+ hematopoietic progenitors can be transfected with mRNA and induce antigen-specific cytotoxic T cell responses*1. J Immunol Meth. 2004;285:171–80.
  • Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, . Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood. 2001;98:49–56.
  • Mosca PJ, Lyerly HK, Clay TM, Morse MA, Lyerly HK. Dendritic cell vaccines. Front Biosci. 2007;12:4050–60.
  • Steinman RM, Dhodapkar M. Active immunization against cancer with dendritic cells: the near future. Int J Cancer. 2001;94:459–73.
  • Guo Y, Wu M, Chen H, Wang X, Liu G, Li G, . Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science. 1994;263:518–20.
  • Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med. 1997;3:558–61.
  • Davidson RL, Gerald PS. Improved techniques for the induction of mammalian cell hybridization by polyethylene glycol. Somatic Cell Genet. 1976;2:165–76.
  • Finaz C, Lefevre A, Teissie J. Electrofusion. A new, highly efficient technique for generating somatic cell hybrids. Exp Cell Res. 1984;150:477–82.
  • Akasaki YKT, 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: 106–13.
  • 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 Nov 7;2:15–26.
  • Lindner M, Schirrmacher V. Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylene-glycol versus electro-fusion protocols. Eur J Clin Invest. 2002;32:207–17.
  • Orentas RJ, Schauer D, Bin Q, Johnson BD. Electrofusion of a weakly immunogenic neuroblastoma with dendritic cells produces a tumor vaccine. Cellular Immunol. 2001;213:4–13.
  • Cao X, Zhang W, Wang J, 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;97:616–25.
  • Kawada M, Ikeda H, Takahashi T, Ishizu A, Ishikura H, Katoh H, . Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo. Int J Cancer. 2003;105:520–6.
  • Kim GY, Chae HJ, Kim KH, Yoon MS, Lee KS, Lee CM, . Dendritic cell-tumor fusion vaccine prevents tumor growth in vivo. Biosci Biotechnol Biochem. 2007 Jan;71(1):215–21.
  • Lespagnard L, Mettens P, Verheyden AM, Tasiaux N, Thielemans K, van Meirvenne S, . Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor immunity. Int J Cancer. 1998;76:250–8.
  • Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol. 1998;161:5516–24.
  • Zhang JK, Li J, Zhang J, Chen HB, Chen SB. Antitumor immunopreventive and immunotherapeutic effect in mice induced by hybrid vaccine of dendritic cells and hepatocarcinoma in vivo. World J Gastroenterol. 2003;9:479–84.
  • Galea-Lauri J, Darling D, Mufti G, Harrison P, Farzaneh F. Eliciting cytotoxic T lymphocytes against acute myeloid leukemia-derived antigens: evaluation of dendritic cell–leukemia cell hybrids and other antigen-loading strategies for dendritic cell-based vaccination. Cancer Immunol Immunother. 2002;51:299–310.
  • Kokhaei P, Rezvany MR, Virving L, Choudhury A, Rabbani H, Osterborg A, . Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL. Leukemia. 2003;17:894–9.
  • 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;27:265–72.
  • Yasuda T, Kamigaki T, Nakamura T, Imanishi T, Hayashi S, Kawasaki K, . Dendritic cell–tumor cell hybrids enhance the induction of cytotoxic T lymphocytes against murine colon cancer: a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells. Oncol Rep. 2006;16:1317–24.
  • Kao JY, Zhang M, Chen CM, Chen JJ. Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pulsed dendritic cell vaccine in colon cancer. Immunol Lett. 2005;101:154–9.
  • Draube A, Beyer M, Schumer S, Thomas RK, Tresckow B, Koslowsky TC, . Efficient activation of autologous tumor-specific T cells: a simple coculture technique of autologous dendritic cells compared to established cell fusion strategies in primary human colorectal carcinoma. J Immunother (1997). 2007;30:359–69.
  • 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; 174:1274–80.
  • Takagi Y, Kikuchi T, Niimura M, Ohno T. Anti-tumor effects of dendritic and tumor cell fusions are not dependent on expression of MHC class I and II by dendritic cells. Cancer Lett. 2004;213:49–55.
  • Xia J, Tanaka Y, Koido S, Liu C, Mukherjee P, Gendler SJ, . Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells. J Immunol. 2003;170:1980–6.
  • 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;101:192–200.
  • Lee WT, Shimizu K, Kuriyama H, Tanaka H, Kjaergaard J, Shu S. Tumor-dendritic cell fusion as a basis for cancer immunotherapy. Otolaryngol Head Neck Surg. 2005;132:755–64.
  • Tanaka H, Shimizu K, Hayashi T, Shu S. Therapeutic immune response induced by electrofusion of dendritic and tumor cells. Cell Immunol. 2002;220:1–12.
  • Gong J, Apostolopoulos V, Chen D, Chen H, Koido S, Gendler SJ, . Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells. Immunology. 2000;101:316–24.
  • 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;168:2111–7.
  • 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;26:757–63.
  • Gong J, Koido S, Chen D, Tanaka Y, Huang L, Avigan D, . Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood. 2002;99:2512–7.
  • Hayashi T, Tanaka H, Tanaka J, Wang R, Averbook BJ, Cohen PA, . Immunogenicity and therapeutic efficacy of dendritic–tumor hybrid cells generated by electrofusion. Clin Immunol. 2002;104:14–20.
  • Iinuma H, Okinaga K, Fukushima R, Inaba T, Iwasaki K, Okinaga A, . Superior protective and therapeutic effects of IL-12 and IL-18 gene-transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma. J Immunol. 2006;176:3461–9.
  • Zhang HM, Zhang LW, Liu WC, Cheng J, Si XM, Ren J. Comparative analysis of DC fused with tumor cells or transfected with tumor total RNA as potential cancer vaccines against hepatocellular carcinoma. Cytotherapy. 2006;8:580–8.
  • Ko E, Luo W, Peng L, Wang X, Ferrone S. Mouse dendritic–endothelial cell hybrids and 4-1BB costimulation elicit antitumor effects mediated by broad antiangiogenic immunity. Cancer Res. 2007;67:7875–84.
  • 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;103:156–64.
  • 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;33:897–904.
  • Du Y-C, Lin P, Zhang J, Lu Y-R, Ning Q-Z, Wang Q. Fusion of CpG-ODN-stimulating dendritic cells with Lewis lung cancer cells can enhance anti-tumor immune responses. Tissue Antigens. 2006;67:368–76.
  • Koido S, Hara E, Homma S, Torii A, Mitsunaga M, Yanagisawa S, . Streptococcal preparation OK-432 promotes fusion efficiency and enhances induction of antigen-specific CTL by fusions of dendritic cells and colorectal cancer cells. J Immunol. 2007;178:613–22.
  • Kao JY, Gong Y, Chen CM, Zheng QD, Chen JJ. Tumor-derived TGF-beta reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol. 2003;170:3806–11.
  • Ou X, Cai S, Liu P, Zeng J, He Y, Wu X, . Enhancement of dendritic cell–tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT. J Cancer Res Clin Oncol. 2008 May;134(5):525–33.
  • Savai R, Schermuly RT, Pullamsetti SS, Schneider M, Greschus S, Ghofrani HA, . A combination hybrid-based vaccination/adoptive cellular therapy to prevent tumor growth by involvement of T cells. Cancer Res. 2007;67:5443–53.
  • Savai R, Schermuly RT, Schneider M, Pullamsetti SS, Grimminger F, Seeger W, . Hybrid-primed lymphocytes and hybrid vaccination prevent tumor growth of Lewis lung carcinoma in mice. J Immunother. 2006;29:175–87.
  • Alvarez E, Moga E, Barquinero J, Sierra J, Briones J. Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response. Gene Ther. 2010;17:469–77.
  • Yasuda T, Kamigaki T, Kawasaki K, Nakamura T, Yamamoto M, Kanemitsu K, . Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma. Cancer Immunol Immunother. 2007;56:1025–36.
  • Hu Z, Liu S, Mai X, Hu Z, Liu C. Anti-tumor effects of fusion vaccine prepared by renal cell carcinoma 786-O cell line and peripheral blood dendritic cells of healthy volunteers in vitro and in human immune reconstituted SCID mice. Cell Immunol. 2010;262:112–9.
  • Xu F, Ye Y-J, Liu W, Kong M, He Y, Wang S. Dendritic cell/tumor hybrids enhances therapeutic efficacy against colorectal cancer liver metastasis in SCID mice. Scand J Gastroenterol. 2010;45:707–13.
  • Gong J, Avigan D, Chen D, Wu Z, Koido S, Kashiwaba M, . Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci USA. 2000;97:2715–8.
  • Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, . Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol. 2000;165:1705–11.
  • Scott-Taylor TH, Pettengell R, Clarke I, Stuhler G, La Barthe MC, Walden P, . Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines. Biochim Biophys Acta (BBA) Mol Basis Dis. 2000;1500:265–79.
  • Trevor KT, Cover C, Ruiz YW, Akporiaye ET, Hersh EM, Landais D, . Generation of dendritic cell–tumor cell hybrids by electrofusion for clinical vaccine application. Cancer Immunol Immunother. 2004 Aug;53(8):705–14.
  • 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;51:367–75.
  • Guo G, Chen S, Zhang J, Luo L, Yu J, Dong H, . Antitumor activity of a fusion of esophageal carcinoma cells with dendritic cells derived from cord blood. Vaccine. 2005;23: 5225–30.
  • Koido S, Hara E, Homma S, Namiki Y, Komita H, Takahara A, . Dendritic/pancreatic carcinoma fusions for clinical use: comparative functional analysis of healthy- versus patient-derived fusions. Clin Immunol. 2010;135:384–400.
  • Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sharav T, . Tumour–dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results. Vaccine. 2005;23: 2367–73.
  • Kugler ASG, Walden P, Zöller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, . Regression of human metastatic renal cell carcinoma after vaccination with tumor cell– dendritic cell hybrids. Nature Med. 2000;6:332–6.
  • Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, . Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer. 2000;85:618–26.
  • Bostanci A, Vogel G. Research misconduct. German inquiry finds flaws, not fraud. Science. 2002;298:1531–3.
  • 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; 38:989–94.
  • 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;144:41–7.
  • Marten A, Renoth S, Heinicke T, Albers P, Pauli A, Mey U, . 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;14:483–94.
  • Avigan D, Vasir B, Gong J, Borges V, Wu Z, Uhl L, . Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004;10:4699–708.
  • Avigan DE, Vasir B, George DJ, Oh WK, Atkins MB, McDermott DF, . Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. J Immunother (1997). 2007;30:749–61.
  • 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;50:337–44.
  • Barbuto JA, Ensina LF, Neves AR, Bergami-Santos P, Leite KR, Marques R, . Dendritic cell–tumor cell hybrid vaccination for metastatic cancer. Cancer Immunol Immunother. 2004;53:1111–8.
  • Stuhler G, Walden P. Recruitment of helper T cells for induction of tumour rejection by cytolytic T lymphocytes. Cancer Immunol Immunother. 1994;39:342–5.
  • Mortarini R, Borri A, Tragni G, Bersani I, Vegetti C, Bajetta E, . Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+T cells in melanoma patients receiving interleukin 12. Cancer Res. 2000;60:3559–68.
  • Kikuchi T, Akasaki Y, Abe T, Fukuda T, Saotome H, Ryan JL, . Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J Immunother (1997). 2004;27:452–9.
  • Wei Y, Sticca RP, Holmes LM, Burgin KE, Li J, Williamson J, . Dendritoma vaccination combined with low dose interleukin-2 in metastatic melanoma patients induced immunological and clinical responses. Int J Oncol. 2006;28:585–93.
  • Haenssle HA, Krause SW, Emmert S, Zutt M, Kretschmer L, Schmidberger H, . Hybrid cell vaccination in metastatic melanoma: clinical and immunologic results of a phase I/II study. J Immunother. 2004;27:147–55.
  • Queant S, Sarde CO, Gobert MG, Kadouche J, Roseto A. Antitumor response against myeloma cells by immunization with mouse syngenic dendritoma. Hybridoma (Larchmt). 2005;24:182–8.
  • Rosenblatt J, Wu Z, Vasir B, Zarwan C, Stone R, Mills H, . Generation of tumor-specific T lymphocytes using dendritic cell/tumor fusions and anti-CD3/CD28. J Immunother. 2010;33:155–66.
  • Ahmed A, Jevremovic D, Suzuki K, Kottke T, Thompson J, Emery S, . Intratumoral expression of a fusogenic membrane glycoprotein enhances the efficacy of replicating adenovirus therapy. Gene Ther. 2003;10:1663–71.
  • Bateman A, Bullough F, Murphy S, Emiliusen L, Lavillette D, Cosset FL, . Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Res. 2000;60:1492–7.
  • Bateman AR, Harrington KJ, Kottke T, Ahmed A, Melcher AA, Gough MJ, . Viral fusogenic membrane glycoproteins kill solid tumor cells by nonapoptotic mechanisms that promote cross presentation of tumor antigens by dendritic cells. Cancer Res. 2002;62:6566–78.
  • Diaz RM, Bateman A, Emiliusen L, Fielding A, Trono D, Russell SJ, . A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy. Gene Ther. 2000;7: 1656–63.
  • Errington F, Bateman A, Kottke T, Thompson J, Harrington K, Merrick A, . Allogeneic tumor cells expressing fusogenic membrane glycoproteins as a platform for clinical cancer immunotherapy. Clin Cancer Res. 2006;12:1333–41.
  • Errington F, Jones J, Merrick A, Bateman A, Harrington K, Gough M, . Fusogenic membrane glycoprotein-mediated tumour cell fusion activates human dendritic cells for enhanced IL-12 production and T-cell priming. Gene Ther. 2006;13:138–49.
  • Gomez-Trevino A, Castel S, Lopez-Iglesias C, Cortadellas N, Comas-Riu J, Mercade E. Effects of adenovirus-mediated SV5 fusogenic glycoprotein expression on tumor cells. J Gene Med. 2003;5:483–92.
  • Higuchi H, Bronk SF, Bateman A, Harrington K, Vile RG, Gores GJ. Viral fusogenic membrane glycoprotein expression causes syncytia formation with bioenergetic cell death: implications for gene therapy. Cancer Res. 2000;60:6396–402.
  • Larmonier N, Merino D, Nicolas A, Cathelin D, Besson A, Bateman A, . Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loading. Apoptosis. 2006;11:1513–24.
  • Linardakis E, Bateman A, Phan V, Ahmed A, Gough M, Olivier K, . Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell–tumor cell fusion. Cancer Res. 2002;62:5495–504.
  • Zhang J, Frolov I, Russell SJ. Gene therapy for malignant glioma using Sindbis vectors expressing a fusogenic membrane glycoprotein. J Gene Med. 2004;6:1082–91.
  • Phan V, Errington F, Cheong SC, Kottke T, Gough M, Altmann S, . A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat Med. 2003;9:1215–9.
  • Cheong SC, Blangenois I, Franssen JD, Servais C, Phan V, Trakatelli M, Bruyns C, Vile R, Velu T, Brandenburger A. Generation of cell hybrids via a fusogenic cell line. J Gene Med. 2006;8:919–28.
  • Morse MA, Clay TM, Mosca P, Lyerly HK. Immunoregulatory T cells in cancer immunotherapy. Expert Opin Biol Ther. 2002;2:827–34.
  • Kalinski P, Okada H. Polarized dendritic cells as cancer vaccines: directing effector-type T cells to tumors. Sem Immunol.22:173–82.
  • Rosenberg SA, Sportes C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, . IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006;29:313–9.
  • Koido S, Tanaka Y, Tajiri H, Gong J. Generation and functional assessment of antigen-specific T cells stimulated by fusions of dendritic cells and allogeneic breast cancer cells. Vaccine. 2007;25:2610–9.
  • Zhang Y, Ma B, Zhou Y, Zhang M, Qiu X, Sui Y, . Dendritic cells fused with allogeneic breast cancer cell line induce tumor antigen-specific CTL responses against autologous breast cancer cells. Breast Cancer Res Treat. 2007 Nov; 105(3):277–86.
  • Neves AR, Ensina LF, Anselmo LB, Leite KR, Buzaid AC, Camara-Lopes LH, . Dendritic cells derived from metastatic cancer patients vaccinated with allogeneic dendritic cell–autologous tumor cell hybrids express more CD86 and induce higher levels of interferon-gamma in mixed lymphocyte reactions. Cancer Immunol Immunother. 2005 Jan;54(1):61–6.
  • 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;170:5317–25.
  • Raje N, Hideshima T, Davies FE, Chauhan D, Treon SP, Young G, . Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma. Br J Haematol. 2004;125:343–52.
  • Soruri A, Fayyazi A, Neumann C, Schlott T, Jung T, Matthes C, . Ex vivo generation of human anti-melanoma autologous cytolytic T cells by dendritic cell/melanoma cell hybridomas. Cancer Immunol Immunother. 2001;50:307–14.
  • Vasir B, Borges V, Wu Z, Grosman D, Rosenblatt J, Irie M, . Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation. Br J Haematol. 2005;129:687–700.
  • Chan RC, Xie H, Zhao GP, Xie Y. Dendritomas formed by fusion of mature dendritic cells with allogenic human hepatocellular carcinoma cells activate autologous cytotoxic T lymphocytes. Immunol Lett. 2002;83:101–9.
  • 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: 177–83.
  • Koido S, Hara E, Homma S, Torii A, Toyama Y, Kawahara H, . 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;11:7891–900.
  • Koido S, Hara E, Torii A, Homma S, Toyama Y, Kawahara H, . 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 Nov 20;117(4):587–95.

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