Butterfield Lisa H, Gooding William, Whiteside Theresa L
Department of Medicine, Surgery and Immunology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
J Immunother. 2008 Jan;31(1):89-100. doi: 10.1097/CJI.0b013e318158fce0.
The development of potency assays for characterization of cellular products used for human therapy throughout early-phase clinical trials is recommended by FDA. We present the results of the development of a standardized IL-12p70 production assay, which is applicable to small samples or large lots of dendritic cell (DC) vaccines generated under a variety of conditions. The assay measures the DC ability to secrete IL-12p70 and respond to helper T-cell signals (CD40L) with or without additional innate immunity signals. It then quantifies IL-12p70 using an immunobead multiplex platform. This 2-step functional assay provides a controlled, reproducible, robust, and cost-effective potency measure for human DC. It discriminates between DC matured in the presence of different cytokine cocktails and between DC obtained from normal donors and patients with human immunodeficiency virus-1 or cancer. It defines the stability of DC vaccines. It's application to DC assessments in several on-going early-phase clinical trials is expected to provide data defining the assay value in predicting in vivo efficacy of DC-based vaccines.
美国食品药品监督管理局（FDA）建议在早期临床试验中开发效价测定方法，以表征用于人类治疗的细胞产品。我们展示了一种标准化的IL-12p70产生测定方法的开发结果，该方法适用于在各种条件下产生的小样本或大量树突状细胞（DC）疫苗。该测定方法测量DC分泌IL-12p70的能力，以及在有或没有额外先天免疫信号的情况下对辅助性T细胞信号（CD40L）的反应。然后使用免疫珠多重平台对IL-12p70进行定量。这种两步功能测定方法为人类DC提供了一种可控、可重复、稳健且具有成本效益的效价测量方法。它可以区分在不同细胞因子混合物存在下成熟的DC，以及从正常供体和患有人类免疫缺陷病毒-1或癌症的患者获得的DC。它定义了DC疫苗的稳定性。预计将其应用于正在进行的几项早期临床试验中的DC评估，将提供数据来定义该测定方法在预测基于DC的疫苗体内疗效方面的价值。
