title: Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis.
abstract: Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70-95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies.
authors.affiliation: Department of Food and Nutrition, Providence University, Taichung, Taiwan, R. O. C; Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R. O. C.
authors.forename: Wei Ting
authors.initials: WT
authors.lastname: Chang
authors.affiliation: Development Center for Biotechnology, New Taipei City, Taiwan, R. O. C.
authors.forename: Tzung Hsien
authors.initials: TH
authors.lastname: Lai
authors.affiliation: Development Center for Biotechnology, New Taipei City, Taiwan, R. O. C.
authors.forename: Yau Jan
authors.initials: YJ
authors.lastname: Chyan
authors.affiliation: Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R. O. C.
authors.forename: Shu Yi
authors.initials: SY
authors.lastname: Yin
authors.affiliation: Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R. O. C.
authors.forename: Yung Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R. O. C.
authors.forename: Wen Chi
authors.initials: WC
authors.lastname: Wei
authors.affiliation: Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, R. O. C.
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology* / Q000601:surgery; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010946:Plants, Medicinal / Q000737:chemistry*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D011134:Polysaccharides
references.citation: Nat Med. 1999 Jul;5(7):774-9
references.pmid: 10395322
references.citation: J Immunol. 2007 Apr 1;178(7):4222-9
references.pmid: 17371978
references.citation: Blood. 2004 Oct 15;104(8):2235-46
references.pmid: 15231572
references.citation: Annu Rev Immunol. 1996;14:233-58
references.pmid: 8717514
references.citation: J Exp Med. 1982 Mar 1;155(3):768-82
references.pmid: 6801178
references.citation: Blood. 2011 Jun 16;117(24):6542-51
references.pmid: 21493800
references.citation: J Ethnopharmacol. 2012 Apr 10;140(3):614-23
references.pmid: 22326673
references.citation: Biochem Biophys Res Commun. 2004 Aug 6;320(4):1103-11
references.pmid: 15249203
references.citation: PLoS One. 2012;7(3):e33678
references.pmid: 22442708
references.citation: J Exp Med. 1998 Mar 2;187(5):693-702
references.pmid: 9480979
references.citation: J Invest Dermatol. 2009 Mar;129(3):573-83
references.pmid: 18843294
references.citation: Trends Biotechnol. 2013 Dec;31(12):668-77
references.pmid: 24125745
references.citation: Curr Opin HIV AIDS. 2010 Sep;5(5):409-13
references.pmid: 20978382
references.citation: J Immunol. 2012 Oct 1;189(7):3397-403
references.pmid: 22914049
references.citation: Nat Med. 2004 May;10(5):475-80
references.pmid: 15122249
references.citation: Evid Based Complement Alternat Med. 2013;2013:932040
references.pmid: 23935688
references.citation: J Exp Clin Cancer Res. 2010 Oct 22;29:137
references.pmid: 20969765
references.citation: Annu Rev Immunol. 2014;32:659-702
references.pmid: 24655300
references.citation: Science. 2006 Sep 29;313(5795):1960-4
references.pmid: 17008531
references.citation: J Immunother. 2008 Sep;31(7):620-32
references.pmid: 18600182
references.citation: Cancer Lett. 2007 Jul 8;252(1):43-54
references.pmid: 17223259
references.citation: J Hematol Oncol. 2009 Jun 10;2:25
references.pmid: 19515245
references.citation: Cancer Res. 2008 Apr 1;68(7):2471-8
references.pmid: 18381456
references.citation: Ann Oncol. 2012 Oct;23 Suppl 7:vii11-9
references.pmid: 22997442
references.citation: J Exp Med. 2004 Nov 15;200(10):1231-41
references.pmid: 15534368
references.citation: Nature. 1998 Jun 4;393(6684):474-8
references.pmid: 9624003
references.citation: Immunol Rev. 2006 Jun;211:214-24
references.pmid: 16824130
references.citation: N Engl J Med. 2005 May 5;352(18):1839-42
references.pmid: 15872196
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8029-34
references.pmid: 17483450
references.citation: Cancer Res. 2009 Dec 1;69(23):9012-9
references.pmid: 19903852
references.citation: Future Oncol. 2012 Oct;8(10):1273-99
references.pmid: 23130928
references.citation: Int J Biol Macromol. 2012 May 1;50(4):891-4
references.pmid: 22285989
references.citation: J Ethnopharmacol. 2012 Feb 15;139(3):788-95
references.pmid: 22212503
references.citation: Expert Rev Vaccines. 2007 Apr;6(2):267-83
references.pmid: 17408375
references.citation: J Clin Invest. 2002 Jun;109(12):1519-26
references.pmid: 12070296
references.citation: Nature. 2006 Apr 13;440(7086):890-5
references.pmid: 16612374
references.citation: Endocr Metab Immune Disord Drug Targets. 2009 Dec;9(4):328-43
references.pmid: 19857199
references.citation: Eur J Immunol. 1997 Dec;27(12):3135-42
references.pmid: 9464798
references.citation: Cell Rep. 2012 Sep 27;2(3):568-79
references.pmid: 22999938
references.citation: Brain Behav Immun. 2003 Feb;17 Suppl 1:S27-36
references.pmid: 12615183
references.citation: Shock. 2014 Mar;41(3):250-5
references.pmid: 24296433
references.citation: Exp Cell Res. 2011 Sep 10;317(15):2210-21
references.pmid: 21741972
references.citation: Nutr J. 2010 Nov 18;9:54
references.pmid: 21087484
references.citation: Nat Rev Cancer. 2004 Jan;4(1):11-22
references.pmid: 14708024
references.citation: Carbohydr Res. 2005 Jan 17;340(1):115-30
references.pmid: 15620674
references.citation: Ann Oncol. 2006 Apr;17(4):563-70
references.pmid: 16418308
references.citation: Cancer Immunol Immunother. 2012 Nov;61(11):1989-2002
references.pmid: 22527248
references.citation: Int J Biol Macromol. 2014 Mar;64:257-66
references.pmid: 24325861
references.citation: J Transl Med. 2006 Aug 16;4:36
references.pmid: 16914047
references.citation: Adv Cancer Res. 2008;99:363-407
references.pmid: 18037410
references.citation: Nature. 1997 Jun 12;387(6634):713-7
references.pmid: 9192897
references.citation: J Immunol. 2011 Jun 15;186(12):6848-59
references.pmid: 21551364
references.citation: Semin Immunol. 2010 Jun;22(3):155-61
references.pmid: 20488726
references.citation: Oncotarget. 2011 Oct;2(10):739-51
references.pmid: 22036896
references.citation: Nat Immunol. 2006 Dec;7(12):1258-65
references.pmid: 17110942
references.citation: Mol Cancer. 2014 Feb 24;13:34
references.pmid: 24565056
references.citation: J Immunol. 2003 Apr 1;170(7):3812-8
references.pmid: 12646648
references.citation: J Immunol. 2000 Dec 1;165(11):6047-55
references.pmid: 11086036
references.citation: J Leukoc Biol. 2005 Jul;78(1):167-77
references.pmid: 15831559
references.citation: Ann Med. 2006;38(4):242-51
references.pmid: 16754255
references.citation: J Exp Med. 2002 May 20;195(10):1257-66
references.pmid: 12021306
references.citation: Front Immunol. 2013 Apr 03;4:82
references.pmid: 23565116
references.citation: Cancer Res. 2011 Nov 15;71(22):6997-7009
references.pmid: 21948969
references.citation: Br J Cancer. 2001 Aug 17;85(4):490-2
references.pmid: 11506484
references.citation: J Immunol. 2011 Apr 15;186(8):4599-608
references.pmid: 21389258
references.citation: Semin Immunol. 1998 Dec;10(6):443-8
references.pmid: 9826577
references.citation: Nature. 1998 Jun 4;393(6684):480-3
references.pmid: 9624005
references.citation: J Clin Oncol. 2007 Aug 20;25(24):3680-7
references.pmid: 17704416
references.citation: Ann Surg. 2009 May;249(5):727-34
references.pmid: 19387333
references.citation: Int J Radiat Biol. 2013 Jan;89(1):16-25
references.pmid: 22856538