Literature DB >> 22728711

Immunostimulatory and anti-neoplasm effects of a novel palindrome CpG oligodeoxynucleotide in mice.

Hai-yan Du1, Li-hou Dong, Bi-jun Zhao, Jie Fu, Qing-qing Wang, Fang Chen, Lun Ou, Na Li, Xiao Sun, Zhong-ming Tang, Hai-feng Song.   

Abstract

AIM: DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODN10, in tumor-bearing mice.
METHODS: B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODN10 or conventional CpG ODN1826 on the indicated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lymphocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were determined using [(3)H]-thymidine incorporation assay, 4-h (51)Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4 and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry.
RESULTS: ODN10 (1, 5 and 25 mg/kg) significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with ODN1826. The immune status was suppressed in tumor-bearing mice. Both ODN10 and ODN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lymphocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting IL-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODN10 presented more potent activity, and displayed the most prominent immunostimulatory potential.
CONCLUSION: ODN10 produces prominent immunomodulatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Th1-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.

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Year:  2012        PMID: 22728711      PMCID: PMC4011330          DOI: 10.1038/aps.2012.54

Source DB:  PubMed          Journal:  Acta Pharmacol Sin        ISSN: 1671-4083            Impact factor:   6.150


  31 in total

Review 1.  Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates.

Authors:  Daniela Verthelyi; Dennis M Klinman
Journal:  Clin Immunol       Date:  2003-10       Impact factor: 3.969

Review 2.  Immunotherapeutic uses of CpG oligodeoxynucleotides.

Authors:  Dennis M Klinman
Journal:  Nat Rev Immunol       Date:  2004-04       Impact factor: 53.106

3.  CpG-A-induced monocyte IFN-gamma-inducible protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha.

Authors:  Sue E Blackwell; Arthur M Krieg
Journal:  J Immunol       Date:  2003-04-15       Impact factor: 5.422

4.  Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma.

Authors:  J E Wooldridge; Z Ballas; A M Krieg; G J Weiner
Journal:  Blood       Date:  1997-04-15       Impact factor: 22.113

5.  Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA.

Authors:  Z K Ballas; W L Rasmussen; A M Krieg
Journal:  J Immunol       Date:  1996-09-01       Impact factor: 5.422

6.  Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities.

Authors:  Jörg Vollmer; Risini Weeratna; Paul Payette; Marion Jurk; Christian Schetter; Meike Laucht; Tanja Wader; Sibylle Tluk; Ming Liu; Heather L Davis; Arthur M Krieg
Journal:  Eur J Immunol       Date:  2004-01       Impact factor: 5.532

7.  CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations.

Authors:  Heidi H van Ojik; Lisette Bevaart; Christopher E Dahle; Annie Bakker; Marco J H Jansen; Martine J van Vugt; Jan G J van de Winkel; George J Weiner
Journal:  Cancer Res       Date:  2003-09-01       Impact factor: 12.701

8.  Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions.

Authors:  Jason D Marshall; Karen Fearon; Christi Abbate; Sandhya Subramanian; Priscilla Yee; Josh Gregorio; Robert L Coffman; Gary Van Nest
Journal:  J Leukoc Biol       Date:  2003-06       Impact factor: 4.962

9.  Intra-tumoral injection of CpG results in the inhibition of tumor growth in murine Colon-26 and B-16 tumors.

Authors:  Sanjay Sharma; Constantine P Karakousis; Hiroshi Takita; Kyu Shin; Stephen P Brooks
Journal:  Biotechnol Lett       Date:  2003-01       Impact factor: 2.461

10.  TLR9 signals after translocating from the ER to CpG DNA in the lysosome.

Authors:  Eicke Latz; Annett Schoenemeyer; Alberto Visintin; Katherine A Fitzgerald; Brian G Monks; Cathrine F Knetter; Egil Lien; Nadra J Nilsen; Terje Espevik; Douglas T Golenbock
Journal:  Nat Immunol       Date:  2004-01-11       Impact factor: 25.606

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  2 in total

1.  Antitumor and Antimetastatic Effect of Small Immunostimulatory RNA against B16 Melanoma in Mice.

Authors:  Tatyana O Kabilova; Aleksandra V Sen'kova; Valeriy P Nikolin; Nelly A Popova; Marina A Zenkova; Valentin V Vlassov; Elena L Chernolovskaya
Journal:  PLoS One       Date:  2016-03-16       Impact factor: 3.240

2.  Molecular Mechanism of the Antiproliferative Activity of Short Immunostimulating dsRNA.

Authors:  Mikhail I Zharkov; Marina A Zenkova; Valentin V Vlassov; Elena L Chernolovskaya
Journal:  Front Oncol       Date:  2019-12-20       Impact factor: 6.244

  2 in total

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