Potency of Mature CD40L RNA Electroporated Dendritic Cells Correlates With IL-12 Secretion by Tracking Multifunctional CD8+/CD28+ Cytotoxic T-cell Responses In Vitro

被引:35
作者
DeBenedette, Mark A. [1 ]
Calderhead, David M. [1 ]
Tcherepanova, Irina Y. [1 ]
Nicolette, Charles A. [1 ]
Healey, Don G. [1 ]
机构
[1] Argos Therapeut Inc, Res Dept, Durham, NC 27704 USA
关键词
dendritic cells; cytotoxic T cells; cell activation; memory; VACCINE REGIMEN; PROSTATE-CANCER; SIPULEUCEL-T; CTL RESPONSE; 3RD SIGNAL; MEMORY; ANTIGEN; ACTIVATION; EFFECTOR; NAIVE;
D O I
10.1097/CJI.0b013e3181fb651a
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Electroporation of mature dendritic cells (DC) with RNA-encoding CD40L greatly enhances the production of interleukin (IL)-12, a proinflammatory cytokine necessary for the induction of T-cell immunity. Results presented herein reveal a correlation between the priming of CD28(+) antigen-reactive effector memory cytotoxic T lymphocytes (CTL) displaying 3 or 4 simultaneous effector functions and the quantity of IL-12 produced by postmaturation electroporation-CD40L DC. By using multiparameter flow cytometry, the quantities of IL-12 needed to prime naive antigen-reactive T cells to simultaneously produce interferon-gamma and tumor necrosis factor-alpha in the presence or absence of IL-2 secretion in conjunction with lytic activity defined by CD107a expression can be used to determine the overall potency of a DC product. In the presence of IL-12, CTL differentiation toward lytic function is not accompanied by a reduction in the secretion of interferon-gamma and tumor necrosis factor-alpha. Therefore, by measuring the availability of IL-12 one can predict the potency of a DC immunotherapeutics in relation to its ability to drive distinct effector memory CTL subsets with multifunctional activities.
引用
收藏
页码:45 / 57
页数:13
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