Umbilical cord blood-derived CD11c+ dendritic cells could serve as an alternative allogeneic source of dendritic cells for cancer immunotherapy
Tóm tắt
Allogenic dendritic cells (DCs) generated from healthy donors, who are complete or partially HLA-matched, have been used for clinical trials. One of the sources for allogenic DCs is umbilical cord blood (UCB) cells. However, as far as cord blood cells are concerned, looking at their naïve nature, there is a concern as to whether the DCs generated from them will have enough potential to elicit a proper T cell response. For this, we compared CD11c+ UCB-DCs/ Cytotoxic T lymphocytes (CTLs) with the conventional source, i.e. peripheral blood (PBL) monocyte DCs/CTLs, using various parameters. CD11c+ DCs generated from the two sources were compared morphologically, phenotypically and functionally. Functional assays included antigen uptake, chemotactic migration and MLR (mixed lymphocyte reaction). The CTLs generated were examined for the activation markers, granzyme A & granzyme B, and IFN-γ secretion. MUC1 (STAPPVHNV) peptide-specific CTLs were quantified by Streptamer staining. In vitro CTL activity was assessed by their efficiency in killing MCF-7 cells. For in vivo CTL assay, a xenograft of MCF-7-luc-F5 cells in female NOD/SCID mice was employed. Regression of tumors in mice was monitored using an in vivo imaging system before and after ten days of CTL infusion. Statistical analysis of all the experiments between the two groups was evaluated by one-way ANOVA. The CD11c+ DCs from the two sources were morphologically and phenotypically similar. Their capacity to uptake antigen, migration towards CCL-19 and MLR activity were equivalent. UCB-CTLs had significantly higher levels of activation markers, number of MUC1 specific CTLs, IFN-γ secretion and IL-12p70/IL-10 ratio than that of PBL-CTLs. Hematoxylin and Eosin-stained tumor sections showed T cell infiltration, which was further confirmed by immunofluorescence staining. In vivo CTL activity was found to be similar with the two sources. Our data demonstrate that CD11c+ UCB-DCs/CTLs are as potent as standard CD11c+ PBL-DC/CTLs and could therefore be used as an allogenic source for therapeutic purposes. The findings of this study could help in taking us one step closer towards the personalized therapy using DC based cancer vaccines.
Tài liệu tham khảo
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