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Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis.

Chang WT, Lai TH, Chyan YJ, Yin SY, Chen YH, Wei WC, Yang NS - PLoS ONE (2015)

Bottom Line: Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Flow cytometric analysis of expression of surface markers on DCs with different treatments.(A) Phenotypic changes in expression of CD40, CD80 and CD86 maturation markers in TCL-loaded DCs as a response to treatment with Cp, Am or [Am+Cp] phytoextracts, all at a concentration of 200 μg/ml. Anti-CD40, CD80 or CD86 antibodies were conjugated with FITC. (B) The mean fluorescence intensity (MFI) of (B[a]) CD40, (B[b]) CD80, or (B[c]) CD86 in DCs from different groups were calculated and are presented as a bar chart. Data represent the mean ± SD obtained from three independent experiments. A P value of less than 0.05 was considered significant (*, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s, no significance).
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pone.0122374.g003: Flow cytometric analysis of expression of surface markers on DCs with different treatments.(A) Phenotypic changes in expression of CD40, CD80 and CD86 maturation markers in TCL-loaded DCs as a response to treatment with Cp, Am or [Am+Cp] phytoextracts, all at a concentration of 200 μg/ml. Anti-CD40, CD80 or CD86 antibodies were conjugated with FITC. (B) The mean fluorescence intensity (MFI) of (B[a]) CD40, (B[b]) CD80, or (B[c]) CD86 in DCs from different groups were calculated and are presented as a bar chart. Data represent the mean ± SD obtained from three independent experiments. A P value of less than 0.05 was considered significant (*, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s, no significance).

Mentions: Based on the findings of the in vivo study (Fig 2), we next evaluated the functional effect of Cp, Am and [Am+Cp] on mouse DCs. Maturation activity is an essential requirement for DCs to prime T cells and induce potent immune responses, we hence assayed the phenotypic changes of three specific molecular markers (CD40, CD80 and CD86) for maturation of DCs. DCs treated with TCL alone (i.e., DC+TCL) were not able to induce DC maturation (Fig 3). In combination with Cp, Am or [Am+Cp], the TCL-loaded DCs showed significantly increased expression of CD40, CD80 and CD86, with a 1.7- to 4.5-fold increase over that of the control group cells (DC+TCL). Among these three groups, Am treatment (DC+TCL+Am) resulted in the most significant increase in CD40 expression, whereas expressions of CD80 and CD86 markers were most upregulated in the Cp group (DC+TCL+Cp). Importantly, all the levels of stimulatory activity were similar or higher than those detected for the positive control (+LPS) group.


Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis.

Chang WT, Lai TH, Chyan YJ, Yin SY, Chen YH, Wei WC, Yang NS - PLoS ONE (2015)

Flow cytometric analysis of expression of surface markers on DCs with different treatments.(A) Phenotypic changes in expression of CD40, CD80 and CD86 maturation markers in TCL-loaded DCs as a response to treatment with Cp, Am or [Am+Cp] phytoextracts, all at a concentration of 200 μg/ml. Anti-CD40, CD80 or CD86 antibodies were conjugated with FITC. (B) The mean fluorescence intensity (MFI) of (B[a]) CD40, (B[b]) CD80, or (B[c]) CD86 in DCs from different groups were calculated and are presented as a bar chart. Data represent the mean ± SD obtained from three independent experiments. A P value of less than 0.05 was considered significant (*, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s, no significance).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4380423&req=5

pone.0122374.g003: Flow cytometric analysis of expression of surface markers on DCs with different treatments.(A) Phenotypic changes in expression of CD40, CD80 and CD86 maturation markers in TCL-loaded DCs as a response to treatment with Cp, Am or [Am+Cp] phytoextracts, all at a concentration of 200 μg/ml. Anti-CD40, CD80 or CD86 antibodies were conjugated with FITC. (B) The mean fluorescence intensity (MFI) of (B[a]) CD40, (B[b]) CD80, or (B[c]) CD86 in DCs from different groups were calculated and are presented as a bar chart. Data represent the mean ± SD obtained from three independent experiments. A P value of less than 0.05 was considered significant (*, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s, no significance).
Mentions: Based on the findings of the in vivo study (Fig 2), we next evaluated the functional effect of Cp, Am and [Am+Cp] on mouse DCs. Maturation activity is an essential requirement for DCs to prime T cells and induce potent immune responses, we hence assayed the phenotypic changes of three specific molecular markers (CD40, CD80 and CD86) for maturation of DCs. DCs treated with TCL alone (i.e., DC+TCL) were not able to induce DC maturation (Fig 3). In combination with Cp, Am or [Am+Cp], the TCL-loaded DCs showed significantly increased expression of CD40, CD80 and CD86, with a 1.7- to 4.5-fold increase over that of the control group cells (DC+TCL). Among these three groups, Am treatment (DC+TCL+Am) resulted in the most significant increase in CD40 expression, whereas expressions of CD80 and CD86 markers were most upregulated in the Cp group (DC+TCL+Cp). Importantly, all the levels of stimulatory activity were similar or higher than those detected for the positive control (+LPS) group.

Bottom Line: Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus