serval:BIB_4CDCB9F2EC57
Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.
10.1371/journal.pone.0028732
000298369100087
22194898
Chiang
C.L.
author
Hagemann
A.R.
author
Leskowitz
R.
author
Mick
R.
author
Garrabrant
T.
author
Czerniecki
B.J.
author
Kandalaft
L.E.
author
Powell
D.J.
author
Coukos
G.
author
article
2011
Plos One
1932-6203
1932-6203
journal
6
12
e28732
"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.
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
eng
60_published
true
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
University of Lausanne
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