City of Hope Lymphoma SPORE

City of Hope淋巴瘤SPORE的总体目标是开展转化研究，以改善霍奇金淋巴瘤和非霍奇金淋巴瘤的治疗。该应用程序包括四个翻译研究项目和四个核心，将开发来自淋巴瘤和T细胞和抗体治疗的分子和免疫学研究的新方法。该补助金中转化研究的一个重要主题是开发有效的淋巴瘤治疗药物，以减少与霍奇金淋巴瘤和非霍奇金淋巴瘤当前治疗方案相关的毒性，可用于治疗老年患者。项目1将研究利用工程化的中央记忆衍生的CD 19特异性T细胞对B细胞淋巴瘤进行细胞免疫治疗的有效性。该项目的研究人员已经开发了一种T细胞遗传修饰平台，用于表达嵌合免疫受体，将中央记忆T细胞的抗原特异性和效应子功能重定向到B细胞淋巴瘤的细胞表面表位，并将在输注后测试这些细胞的持久性和扩增。由于流行病学研究表明，移植前治疗暴露的干细胞损伤可能在随后的骨髓增生异常中发挥作用，项目2将纵向研究霍奇金和非霍奇金淋巴瘤患者人群。研究人员将继续研究预测骨髓增生异常的细胞和分子因素，并确定导致这种治疗并发症的事件的分子序列。在项目3中，研究人员将测试一种分子工程化的新型抗CD 20 IL-2免疫细胞因子，用于治疗0020淋巴瘤患者。这个项目的一个重要组成部分将是描绘在免疫细胞因子介导的抗淋巴瘤体内活性的免疫效应机制。项目4将开发基于siRNA的针对转录因子（STATS）的治疗剂，该转录因子在淋巴瘤行为中很重要，使用抗体导向的环糊精纳米颗粒治疗B细胞淋巴瘤患者。在这个淋巴瘤孢子的项目将由四个核心，包括支持：管理，生物统计学和研究信息学，组织库的分子和细胞研究，和生物制造。这个淋巴瘤孢子还将支持发展研究计划和职业发展计划，以促进试点转化研究项目和年轻研究人员专注于淋巴瘤的进步。

The overall goal of the City of Hope Lymphoma SPORE is to develop translational studies to improve the treatment of Hodgkin and non-Hodgkin lymphoma. This application, consisting of four translational research projects and four cores, will develop novel approaches that are derived from molecular and immunologic studies in lymphoma and T-cell and antibody-based therapies. An important theme of the translational studies in this grant is to develop effective therapeutics for lymphoma that will reduce toxicities associated with current treatment regimens for Hodgkin and non-Hodgkin Lymphoma which can be utilized for treatment of older patients. Project 1 will study the effectiveness of cellular immunotherapy for B cell lymphoma utilizing engineered central memory derived CD19-specific T-cells. Investigators in this project have developed a T-cell genetic modification platform for expressing chimeric immunoreceptors that redirect antigen specificity and effector function of central memory T-cells towards cell surface epitopes on B cell lymphomas and will test the persistence and expansion of these cells after infusion. Because epidemiologic Studies indicate that stem cell damage from pretransplant therapeutic exposures may play a role in the subsequent development of myelodysplasia, Project 2 will longitudinally study a population of patients with Hodgkin and non-Hodgkin Lymphoma. The investigators will continue their studies of the cellular and molecular factors that are predictive for development of myelodysplasia, and to determine the molecular sequence of events that lead to this complication of treatment. In Project 3 investigators will test a molecularly engineered novel anti-CD20 IL-2 immunocytokine for the treatment of patients with 0020"^ lymphoma. An important component of this project will be to delineate the immunologic effector mechanisms operative in immunocytokine-mediated anti-lymphoma in vivo activity. Project 4 will develop siRNA based therapeutics against transcription factors (STATS) important in lymphoma behavior using an antibody directed cyclodextrin nanoparticle for treatment of patients with B cell lymphoma. The projects in this Lymphoma SPORE will be supported by four cores including: Administration, Biostatistics and Research Informatics, Tissue Bank for Molecular and Cellular Studies, and Biological Manufacturing. This Lymphoma SPORE will also support a Developmental Research Program and a Career Development Program to foster the advancement of pilot translational research projects and young investigators focused on lymphoma.