Reviews and Monographs

Reviews and Monographs Progress in Biochemistry and Biophysics 2010, 37(9): 945~950 wwwpibbaccn * - ** ( 650118) (DC) DC DC/ DC DC/ / T DC/ R73 R392 DOI: 103724/SPJ1206201000160 1973 Steinman Cohn [1] HER-2/neu CTL (dendritic cells DC) DC DC Rosenberg [7] 35 (antigen presenting cell APC) T 14 (71%) [2 3] DC DC 1 DC DC DC DC DC Bae [4] DC DC (CEA) T T (CTL) DC Li [5] DC CTL (IFN)-γ Sas [6] HER-2/neu DC HER-2/neu 198 DC * (NCET-08-0923), (30671904), (2009NS017), (2008CC006), ( 07S060202) (2006 PY01-12) ** Tel: 0871-8100739, E-mail: songxin68@yahoocomcn 2010-03-29 2010-05-24

946 Prog Biochem Biophys 2010; 37 (9) DC DC/ Sp2/0 9333% (14/15) 7333% (11/15) DC Ko [18] SVR EC( ) DC EC- CD4 + DC CD8 + T DC [8] PEG DC [9] Gottfried [10] T PEG 4~8 T -C APC MHC / ( DC/ Yasuda [11] 1) T [19] CD80(B7-1) CD86(B7-2)( 2) DC T ( IL-12 IFN-γ ) T Guo [8] [20] IL-12 Goddard [12] DC T INF-γ [21] DC Lee [22] (SCC) DC/ T IL-12 DC T DC/ Shi [23] pcdna-il-12 J558 DC Sp2/0 PBS28 PBS DC DC/J558/IL-12 cells IL-12 2 DC/ CTL IL-12 [24] 21 DC DC/ IL-12 Koido [13] DC MHC- / 22 CD80 CD86 (CEA) DC/ T IFN-γ 5 10 5 CD8 + T [9] CTL / Savai [14] [25 27] [27 31] [32] [33] [34] (LLC) ( 1) 50% 1 Fas caspase-8 Zhou caspase-3 [25] 10 [15] Tamai [16] 6 (SD) 15 Brtbuto T [27] 22 Quéant [17] 3 (PR)( (Sp2/0) 21 ) 14 (SD)

2010; 37 (9) - 947 13 Avigan [34] 50% 8 cm 6 cm 50% 44% 4 3 T INF-γ (CR) [27 31] Trefzer [31] 17 DC / T 14 T (CTL) 8 1 CR 1 PR 6 IFN-γ Berger [35] SD 28 9 5~22 14 125 DC ( 8 ) T DC Kikuchi [33] IL-12 15 4 Table 1 1 1 DC- / Clinical responses of Phase / study of tumor-dc hybrid vaccines in malignant neoplasms DC CR PR MR SD PEG 351%~41% 10 1 6 [25] 200% 24 2 8 [26] 15%~30% 22 3 14 [27] 11 8 PEG 50%~15% 10 1 1 1 [28] / 17 1 1 6 [29] 70%~13% 11 1 [30] 50%~200% 17 1 1 6 [31] PEG 200% 12 3 1 3 [32] PEG 662% 15 4 1 2 [33] / PEG 180%~71% 29 1 1 6 [34] 23 DC- DC ( DC DC) DC Suzuki [37] DC DC DC/ Yasuda [36] Balb/c (H-2d) CT26CL25 DC(Balb/c) M 覿 rten [38] T C57BL/6(H-2b) DC B6D2F1 (H-2b/d) DC/ DC DC DC DC DC/ APC MHC T [39] (75% ) DC NK CD4 + T DC/T HLA- T

948 Prog Biochem Biophys 2010; 37 (9) DC MHC 1255 1261 DC [40] Vasir [41] DC DC Med, 2010, 16(1): 98 105 Neves [42] DC DC IFN-γ Exp Immunol, 2009, 157(1): 128 138 DC 3 DC/ Cancer Gene Ther, 2008, 15(10): 655 666 DC/ DC/ DC T 466(9): 2176 2183 DC/ / 235 240 a DC 2:15 DC/ b c Oncol Rep, 2006, 16(6): 1317 1324 DC ( ) DC DC 131(1): 82 89 DC- [1] Steinman R M, Cohn Z A Identification of a novel cell type in peripheral lymphoid organs of mice Morphology, quantitation, tissue distribution J Exp Med, 1973, 137(5): 1142 1162 [2] Sender L Y, Gibbert K, Suezer Y, et al CD40 ligand-triggered human dendritic cells mount interleukin-23 responses that are further enhanced by danger signals Mol Immunol, 2010, 47 (6): [3] Villablanca E J, Raccosta L, Zhou D, et al Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses Nat [4] Bae M Y, Cho N H, Seong S Y Protective anti-tumour immune responses by murine dendritic cells pulsed with recombinant Tat-carcinoembryonic antigen derived from Escherichia coli Clin [5] Li Y L, Wu Y G, Wang Y Q, et al Bone marrow-derived dendritic cells pulsed with tumor lysates induce anti-tumor immunity against gastric cancer ex vivo World J Gastroenterol, 2008, 14(46): 7127 7132 [6] Sas S, Chan T, Sami A, et al Vaccination of fiber-modified adenovirus-transfected dendritic cells to express HER-2/neu stimulates efficient HER-2/neu-specific humoral and CTL responses and reduces breast carcinogenesis in transgenic mice [7] Rosenberg S A, Yang J C, Restifo N P Cancer immunotherapy: moving beyond current vaccines Nat Med, 2004, 10(9): 909 915 [8] Guo W, Guo Y, Tang S, et al Dendritic cell-ewing's sarcoma cell hybrids enhance antitumor immunity Clin Orthop Relat Res, 2008, [9] Zhang H, Zheng S S, Jiang G P, et al Antitumor effect of immunization with fusion of dendritic cells and hepatocellular carcinoma cells in mice Hepatobiliary Pancreat Dis Int, 2004, 3(2): [10] Gottfried E, Krieg R, Eichelberg C, et al Characterization of cells prepared by dendritic cell-tumor cell fusion Cancer Immun, 2002, [11] Yasuda T, Kamigaki T, Nakamura T, et al 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 [12] Goddard R V, Prentice A G, Copplestone J A, et al 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, [13] Koido S, Hara E, Homma S, et al Synergistic induction of antigenspecific CTL by fusions of TLR-stimulated dendritic cells and heat-stressed tumor cells J Immunol, 2007, 179(7): 4874 4883 [14] Savai R, Schermuly R T, Schneider M, et al Hybrid-primed lymphocytes and hybrid vaccination prevent tumor growth of lewis lung carcinoma in mice J Immunother, 2006, 29(2): 175 187 [15] Savai R, Schermuly R T, Pullamsetti S S, et al A combination hybrid-based vaccination/adoptive cellular therapy to prevent tumor growth by involvement of T cells Cancer Res, 2007, 67(11): 5443

2010; 37 (9) - 949 5453 [16] Tamai H, Watanabe S, Zheng R, et al Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic-tumor hybrid vaccination and adoptive transfer of sensitized T cells Clin Immunol, 2008, 127(1): 66 77 [17] Quéant S, Sarde C O, Gobert M G, et al Antitumor response against myeloma cells by immunization with mouse syngenic dendritoma Hybridoma (Larchmt), 2005, 24(4): 182 188 [18] Ko E, Luo W, Peng L, et al Mouse dendritic-endothelial cell hybrids and 4-1BB costimulation elicit antitumor effects mediated by broad antiangiogenic immunity Cancer Res, 2007, 67 (16): 7875 7884 [19] Janeway C A Jr, Bottomly K Signals and signs for lymphocyte responses Cell, 1994, 76(2): 275 285 [20] Mescher M F, Curtsinger J M, Agarwal P, et al Signals required for programming effector and memory development by CD8 + T cells Immunol Rev, 2006, 211: 81 92 [21] Giermasz A S, Urban J A, Nakamura Y, et al Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines Cancer Immunol Immunother, 2009, 58(8): 1329 [22] Lee W T, Tamai H, Cohen P, et al Immunotherapy of established murine squamous cell carcinoma using fused dendritic-tumor cell hybrids Arch Otolaryngol Head Neck Surg, 2008, 134(6): 608 613 [23] Shi M, Su L, Hao S, et al Fusion hybrid of dendritic cells and engineered tumor cells expressing interleukin-12 induces type 1 immune responses against tumor Tumori, 2005, 91(6): 531 538 [24] Vasir B, Wu Z, Crawford K, et al Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-cd3/cd28 promotes the expansion of activated tumor reactive cells J Immunol, 2008, 181(1): 808 821 [25] Zhou J, Weng D, Zhou F, et al Patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor activity: in vitro results and clinical responses Cancer Immunol Immunother, 2009, 58(10): 1587 1597 [26] Avigan D E, Vasir B, George D J, et al Phase / study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage renal cell carcinoma J Immunother, 2007, 30(7): 749 761 [27] Barbuto J A, Ensina L F, Neves A R, et al Dendritic cell-tumor cell hybrid vaccination for metastatic cancer Cancer Immunol Immunother, 2004, 53(12): 1111 1118 [28] Wei Y, Sticca R P, Holmes L M, et al Dendritoma vaccination combined with low dose interleukin-2 in metastatic melanoma patients induced immunological and clinical responses Int J Oncol, 2006, 28(3): 585 593 [29] Trefzer U, Herberth G, Wohlan K, et al Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results Vaccine, 2005, 23(17 18): 2367 2373 [30] Haenssle H A, Krause S W, Emmert S, et al Hybrid cell vaccination in metastatic melanoma: clinical and immunologic results of a phase / study J Immunother, 2004, 27(2): 147 155 [31] Trefzer U, Herberth G, Wohlan K, et al Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage and patients Int J Cancer, 2004, 110(5): 730 740 [32] Homma S, Kikuchi T, Ishiji N, et al Cancer immunotherapy by fusions of dendritic and tumour cells and rh-il-12 Eur J Clin Invest, 2005, 35(4): 279 286 [33] Kikuchi T, Akasaki Y, Abe T, et al Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12 J Immunother, 2004, 27(6): 452 459 [34] Avigan D, Vasir B, Gong J, et al Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses Clin Cancer Res, 2004, 10(14): 4699 4708 [35] Berger T G, Haendle I, Schrama D, et al Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells Int J Cancer, 2004, 111(2): 229 237 [36] Yasuda T, Kamigaki T, Kawasaki K, et al 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(7): 1025 1036 [37] Suzuki T, Fukuhara T, Tanaka M, et al Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells Clin Cancer Res, 2005, 11(1): 58 66 [38] M 覿 rten A, Renoth S, Heinicke T, et al 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): 483 494 [39] Tanaka Y, Koido S, Ohana M, et al Induction of impaired antitumor immunity by fusion of MHC class II-deficient dendritic cells with tumor cells J Immunol, 2005, 174(3): 1274 1280 [40] Bennaceur K, Chapman J, Brikci-Nigassa L, et al Dendritic cells dysfunction in tumour environment Cancer Lett, 2008, 272 (2): 186 196 [41] Vasir B, Borges V, Wu Z, et al Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation Br J Haematol, 2005, 129(5): 687 700 [42] Neves A R, Ensina L F, Anselmo L B, et al 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, 54(1): 61 66

950 Prog Biochem Biophys 2010; 37 (9) Progress in Tumor-Dentritic Cell Hybrid Vaccines * CHEN Xiao-Dan, SONG Xin ** (The Third Affiliated Hospital of Kunming Medical College, Yunnan Cancer Hospital, Kunming 650118) Abstract Dendritic cells (DCs) are the most potent professional APCs and play an important role in cancer immune response With the rapid development of DC-based cancer vaccines, tumor-dc hybrids are the most effective ones they could present antigens and keep on producing endogenous antigens The tumor-dc hybrids are currently being evaluated in many animal and clinical trials, available published data showed that hybrids could induce tumor specific T lymphocyte response and be well-tolerated in patients The progress of tumor-dc hybrids, as well as some issues was discussed Key words cancer immunotherapy, dendritic cells, fusion, neoplasm vaccines DOI: 103724/SPJ1206201000160 *This work was supported by grants from New Century Excellent Talent Supporting Project of Ministry of Education of China (NCET-08-0923), The National Natural Science Foundation of China (30671904), Yunnan Provincial Technology Project of Health (2009NS017), Yunnan Provincial Key Program for Applied Basic Research (2008CC006), The Key Program of Science and Technology Project of Kunming(07S060202) and Culture Program for Reserve Talents of Middle-Young Aged Academic and Technology Leader of Yunnan Province of China(2006PY01-12) **Corresponding author Tel: 86-871-8100739, E-mail: songxin68@yahoocomcn Received: March 29, 2010 Accepted: May 24, 2010