Cancer immunotherapeutic effects of novel CpG ODN in murine tumor model

被引:16
作者
Cho, Hyeon Cheol [1 ]
Kim, Bo Hwan [1 ]
Kim, Kyunghoon [4 ]
Park, Ju Youn [1 ]
Chang, Jae-Ho [1 ]
Kim, Soo-Ki [1 ,2 ,3 ]
机构
[1] Yonsei Univ, Wonju Coll Med, Dept Microbiol, Wonju 220701, South Korea
[2] Yonsei Univ, Wonju Coll Med, Inst Lifelong Hlth, Wonju 220701, South Korea
[3] Yonsei Univ, Wonju Coll Med, Inst Basic Med Sci, Wonju 220701, South Korea
[4] Kangwon Natl Univ, Div Life Sci, Coll Nat Sci, Chunchon 200701, South Korea
关键词
CpG ODN; cancer; immunotherapy; NK cell; cytokine;
D O I
10.1016/j.intimp.2008.05.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
White CpG oligodeoxynucleotides (CDN) are excellent candidates for cancer immunotherapeutics, the numbers of usable CpG ODNs are limited in current clinical settings. To resolve this, we investigated whether novel CpG ODN (KSK-CpG) would be an effective immunotherapeutic in a murine tumor model by affecting in vivo and in vitro parameters, such as survival span, the number of tumor nodules, natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activity and interleukin (IL)-6 or IL-12 cytokine release in splenocytes. We found that KSK-CpG was effective in the murine cancer model by way of prolonging survival span, reducing the number of tumor nodules, augmenting NK cell and CTL cytotoxicity, as well as evoking IL-6 and IL-12 cytokine release in splenocytes. Collectively, these data demonstrate that KSK-CpG is active against the highly malignant B16BL6 and EL4 tumor mouse model via innate immune augmentation. Crown Copyright (c) 2008 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1401 / 1407
页数:7
相关论文
共 23 条
[1]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[2]   Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs [J].
Ballas, ZK ;
Krieg, AM ;
Warren, T ;
Rasmussen, W ;
Davis, HL ;
Waldschmidt, M ;
Weiner, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :4878-4886
[3]   Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma [J].
Carpentier, A ;
Laigle-Donadey, F ;
Zohar, S ;
Capelle, L ;
Behin, A ;
Tibi, A ;
Martin-Duverneuil, N ;
Sanson, M ;
Lacomblez, L ;
Taillibert, S ;
Puybasset, L ;
Van Effenterre, R ;
Delattre, JY ;
Carpentier, AF .
NEURO-ONCOLOGY, 2006, 8 (01) :60-66
[4]  
Carpentier AF, 1999, CANCER RES, V59, P5429
[5]   CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity [J].
Chu, RS ;
Targoni, OS ;
Krieg, AM ;
Lehmann, PV ;
Harding, CV .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1623-1631
[6]  
COLIGAN JE, 2000, CURRENT PROTOCOLS IM
[7]   Antitumour effect of OM-174 and Cyclophosphamide on murine B16 melanoma in different experimental conditions [J].
D'Agostini, C ;
Pica, F ;
Febbraro, G ;
Grelli, S ;
Chiavaroli, C ;
Garaci, E .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2005, 5 (7-8) :1205-1212
[8]   Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma:: increased interferon-α/β-inducible gene expression, without significant toxicity [J].
Friedberg, JW ;
Kim, H ;
McCauley, M ;
Hessel, EM ;
Sims, P ;
Fisher, DC ;
Nadler, LM ;
Coffman, RL ;
Freedman, AS .
BLOOD, 2005, 105 (02) :489-495
[9]   Peritumoral CpG DNA elicits a coordinated response of CD8 T cells and innate effectors to cure established tumors in a murine colon carcinoma model [J].
Heckelsmiller, K ;
Rall, K ;
Beck, S ;
Schlamp, A ;
Seiderer, J ;
Jahrsdörfer, B ;
Krug, A ;
Rothenfusser, S ;
Endres, S ;
Hartmann, G .
JOURNAL OF IMMUNOLOGY, 2002, 169 (07) :3892-3899
[10]   CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma [J].
Klinman, DM ;
Yi, AK ;
Beaucage, SL ;
Conover, J ;
Krieg, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2879-2883