Abstract
IntroductionAllogenic 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.MethodsCD11c+ 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.ResultsThe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0160-8) contains supplementary material, which is available to authorized users.
Highlights
Allogenic dendritic cells (DCs) generated from healthy donors, who are complete or partially HLA-matched, have been used for clinical trials
Data generated from this study clearly demonstrate that umbilical cord blood (UCB)-DCs are as potent as their standard vaccine counterparts i.e., peripheral blood (PBL) monocyte DCs, and could be used as an allogenic source for therapeutic applications
UCB and PBL-derived DCs have similar morphology and phenotype DCs were generated from PBL monocytes and UCB mononuclear cells (MNCs) as described earlier
Summary
Allogenic dendritic cells (DCs) generated from healthy donors, who are complete or partially HLA-matched, have been used for clinical trials. Results: 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. Dendritic cells (DCs) are crucial for the induction of both primary and secondary immune responses, as well as for eliciting immunological tolerance Their capacity to effectively cross-present exogenous antigens to T lymphocytes makes DCs essential for the induction of adaptive immune responses against malignant cells. Immunotherapies with allogeneic DCs pulsed with tumor antigens to generate specific T cell responses have been tested in clinical trials with patients having solid tumors as well as in different hematological malignancies [14, 15]. UCB-derived DCs have been used in the pilot phase of clinical trials as well, in hematological disorders like AML, as a therapeutic agent to increase the survival of patients [29, 30]
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