City of Hope Lymphoma SPORE

希望之城淋巴瘤孢子的总体目标是发展转化研究，以改善霍奇金淋巴瘤和非霍奇金淋巴瘤的治疗。该申请由四个转化研究项目和四个核心组成，将开发来自淋巴瘤、t细胞和抗体治疗的分子和免疫学研究的新方法。该资助的转化研究的一个重要主题是开发有效的淋巴瘤治疗方法，以减少与霍奇金淋巴瘤和非霍奇金淋巴瘤目前治疗方案相关的毒性，并可用于治疗老年患者。项目1将研究利用工程化中央记忆衍生的cd19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。该项目的研究人员开发了一种t细胞基因修饰平台，用于表达嵌合免疫受体，将中枢记忆t细胞的抗原特异性和效应功能定向到B细胞淋巴瘤的细胞表面表位，并将测试这些细胞在输注后的持久性和扩增性。由于流行病学研究表明，移植前治疗暴露导致的干细胞损伤可能在骨髓发育不良的后续发展中发挥作用，因此项目2将对霍奇金淋巴瘤和非霍奇金淋巴瘤患者进行纵向研究。研究人员将继续研究预测骨髓发育不良发展的细胞和分子因素，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的新型抗cd20 IL-2免疫细胞因子，用于治疗0020”^淋巴瘤患者。该项目的一个重要组成部分将是描述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的靶向转录因子（STATS）的疗法，使用抗体导向的环糊精纳米颗粒治疗B细胞淋巴瘤患者。该淋巴瘤孢子项目将由四个核心提供支持，包括：行政管理、生物统计和研究信息学、分子和细胞研究组织库以及生物制造。该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的发展，并培养专注于淋巴瘤的年轻研究人员。

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.