Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.

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State: Public
Version: author
Serval ID
serval:BIB_4CDCB9F2EC57
Type
Article: article from journal or magazin.
Collection
Publications
Title
Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.
Journal
Plos One
Author(s)
Chiang C.L., Hagemann A.R., Leskowitz R., Mick R., Garrabrant T., Czerniecki B.J., Kandalaft L.E., Powell D.J., Coukos G.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2011
Volume
6
Number
12
Pages
e28732
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
"Day-7" myeloid DCs are commonly used in the clinic. However, there is a strong need to develop DCs faster that have the same potent immunostimulatory capacity as "Day-7" myeloid DCs and at the same time minimizing time, labor and cost of DC preparations. Although "2 days" DCs can elicit peptide-specific responses, they have not been demonstrated to engulf, process and present complex whole tumor lysates, which could be more convenient and personalized source of tumor antigens than defined peptides. In this preclinical study, we evaluated the T-cell stimulatory capacity of Day-2, Day-4, and Day-7 cultured monocyte-derived DCs loaded with SKOV3 cell whole lysate prepared by freeze-thaw or by UVB-irradiation followed by freeze-thaw, and matured with lipopolysaccharide (LPS) and interferon (IFN)-gamma. DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses. Day-4 and Day-7 DCs exhibited similar phagocytic abilities, which were superior to Day-2 DCs. Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10. Importantly, Day-4 and Day-7 DCs derived from ovarian cancer patients stimulated equally strongly tumor-specific T-cell responses. This is the first study demonstrating the highly immunogenic and strong T-cell stimulatory properties of Day-4 myeloid DCs, and provided important preclinical data for rapid development of potent whole tumor lysate-loaded DC vaccines that are applicable to many tumor types.
Keywords
Cell Differentiation/drug effects, Cell Line, Tumor, Cross-Priming/drug effects, Cytokines/biosynthesis, Dendritic Cells/cytology, Dendritic Cells/drug effects, Female, Health, Humans, Interferon-gamma/pharmacology, Lipopolysaccharides/pharmacology, Myeloid Cells/cytology, Myeloid Cells/drug effects, Ovarian Neoplasms/immunology, Ovarian Neoplasms/pathology, Phagocytosis/drug effects, Phenotype, T-Lymphocytes/cytology, T-Lymphocytes/drug effects, Tissue Donors, Tissue Extracts/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:42
Last modification date
20/08/2019 14:01
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