Immunotherapy of inflammation, autoimmune disease and cancer

炎症、自身免疫性疾病和癌症的免疫治疗

• 批准号: 10487166
• 负责人: Wanjun Chen
• 金额: $ 79.72万
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487166
• 关键词: Animal Model; Antigens; Apoptosis; Autoimmune Diseases; Autoimmunity; Cells; Cellular Metabolic Process; Chronic; Development; Disease; Experimental Animal Model; Experimental Models; Future; Goals; Homeostasis; Immune Tolerance; Immune response; Immune system; Immunity; Immunotherapy; Inflammation; Knowledge; Malignant Neoplasms; Metabolic syndrome; Metabolism; Oral cavity; Pathogenesis; Patients; Regulation; Regulatory T-Lymphocyte; Role; T-Lymphocyte; Therapeutic; Transforming Growth Factor beta; Translating; Tumor Antigens; effector T cell; immune function; macrophage; microbiota; mucosal microbiota; prevent

We utilize the knowledge and information acquired from studying the basic mechanisms of how the immune system interacts with mucosal microbiota, cell metabolism and apoptosis to understand the pathogeneses of autoimmune disease, chronic inflammation and cancer. We then develop more specific and effective immunotherapies to prevent and treat these diseases in the experimental animal models with a goal to translate the immunotherapies to patients with these diseases in the future. Specifically, we have been studying, (1) the effect of the mucosal microbiota in both gut and oral cavity on the development and homeostasis of immune system and consequently on the pathogenesis of autoimmunity, metabolic syndrome and cancer. We explore the possibility of manipulating the composition and diversity of the microbiota to prevent and treat the diseases; (2) investigate the roles of metabolism in the development and function of immune cells including T cells and macrophages. We manipulate the cell metabolism to change the function of immune cells for therapeutic purposes in experimental models of autoimmune diseases and cancer; (3) we study the regulation of cell apoptosis to immune tolerance and immunity, focusing on TGF-beta and regulatory T cells. We manipulate immune responses to develop antigen-specific therapy by inducing antigen-specific regulatory T cells to treat autoimmunity or to generate tumor-antigen-specific T effector cells to treat cancer.

我们利用从研究免疫系统如何与粘膜微生物群，细胞代谢和细胞凋亡相互作用的基本机制中获得的知识和信息来了解自身免疫性疾病，慢性炎症和癌症的发病机制。然后，我们在实验动物模型中开发更特异和有效的免疫疗法来预防和治疗这些疾病，目标是将来将免疫疗法转化为这些疾病的患者。具体而言，我们一直在研究，（1）肠道和口腔中的粘膜微生物群对免疫系统的发育和稳态的影响，从而对自身免疫，代谢综合征和癌症的发病机制的影响。我们探索操纵微生物群的组成和多样性以预防和治疗疾病的可能性;（2）研究代谢在免疫细胞（包括T细胞和巨噬细胞）的发育和功能中的作用。我们在自身免疫性疾病和癌症的实验模型中操纵细胞代谢以改变免疫细胞的功能用于治疗目的;（3）我们研究细胞凋亡对免疫耐受和免疫的调节，重点是TGF-β和调节性T细胞。我们通过诱导抗原特异性调节性T细胞来治疗自身免疫或产生肿瘤抗原特异性T效应细胞来治疗癌症，从而操纵免疫应答以开发抗原特异性治疗。