Biomarkers for Study of Botanical Immunomodulators

免疫系统具有介导针对病原体和肿瘤的特定保护作用的能力。因此，人们对利用免疫系统获得治疗益处的方法非常感兴趣。许多植物类药物通常用于人类，因为它们具有假定的免疫调节作用。然而，无论是在体外还是在体内，这些药物对人类特异性免疫反应的影响仍不清楚。在Livingston、Cheung和Pamer的项目中描述的研究的同时，我们试图定义植物性药物对人类免疫反应的影响。这一目标的实现将指导未来更大规模的临床试验的设计，并对将临床前研究成果转化为临床至关重要。Cassileth项目的目标是识别和表征选定的植物药物在体外和体内对人类免疫反应的影响。我们的工作假设是，口服植物药对人体免疫系统的一些影响可以在体外使用定量分析来模拟，这些测定可能有助于作为体内植物效应的替代标记物，并且在体内补充后对免疫系统可测量的生物效应的检测对于确定它们的活性和了解它们的作用机制都是重要的。我们将测试精选的核心植物药对健康志愿者外周血单个核细胞的影响。同时，选定的植物药物的免疫调节作用也将在早期临床试验的背景下进行体内测试，以确定人类体内的生物标记物。第一次试验将在1-2年内在健康志愿者中进行。将评估对先天免疫和获得性免疫的影响。在研究的后期，来自Livingston、Cheung和Pamer项目的数据将被用于设计早期临床试验，以测试植物类药物在疾病环境中的效果。总体而言，这些数据将为优化评估这些药物的免疫原性和生物效果，以及它们与癌症患者的其他治疗方法(例如，单抗或疫苗)的组合提供框架。具体目标是：1.确定选定的植物药对体外人体免疫反应的影响；2.评估Maitake D组分的免疫调节作用，并在一项小型早期安慰剂对照的双盲临床研究中评估健康志愿者的剂量反应；3.在人类适当疾病环境下的2项早期临床试验的背景下，证实Livingston、Cheung和Pamer的项目中的发现。

The immune system has the capacity to mediate specific protection against pathogens and tumors. Therefore there is great interest in methods to harness the immune system for therapeutic benefit. Many botanicals are commonly utilized in humans for their putative immune-modulatory effects. However, the effects of these agents on specific immune responses in humans, both in vitro and particularly in vivo, remain unclear. In parallel with investigations described under Projects by Livingston, Cheung, and Pamer, we seek to define the effects of botanicals on the human immune response. Accomplishment of this objective will guide the design of larger clinical trials in the future and is essential to the translation of preclinical research findings to the clinic. The objective of Project by Cassileth is to identify and characterize the effects of the selected botanicals on human immune response in vitro and in vivo. Our working hypothesis is that some effects of oral botanicals on the human immune system can be modeled in vitro using quantitative assays, that these assays may be useful as surrogate markers of botanical effects in vivo, and that the detection of measurable biologic effects on the immune system after supplementation in vivo will be important both for defining their activity and for understanding their mechanism of action. We will test the effects of selected core botanicals on peripheral blood mononuclear cells from healthy volunteers. In parallel, immune modulatory effects of selected botanicals will also be tested in vivo in the context of early phase clinical trials to define human in vivo biomarkers. The first trial will be conducted in healthy volunteers in years 1-2. Effects on innate and adaptive immunity will be evaluated. In the later years of the study period, data from projects by Livingston, Cheung, and Pamer will be utilized to design early-phase clinical trials to test the effects of botanicals in disease settings. As a whole, these data will provide the framework for optimal evaluation of immunogenicity and biologic effects of these agents, and their combination with other therapies (eg, monoclonal antibodies or vaccines) in cancer patients. The specific aims are: 1. To characterize the effects of selected botanicals on human immune response in vitro; 2. To evaluate the immunomodulatory effects of Maitake D fraction and assess dose response in a small early phase placebo-controlled, double-blind clinical study in healthy volunteers; 3. To confirm the findings made in Projects by Livingston, Cheung, and Pamer in the context of 2 early-phase clinical trials in appropriate disease settings in human populations.