City of Hope Lymphoma SPORE

描述（由申请人提供）：希望之城淋巴瘤孢子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检测和治疗。该项目由四个转化研究项目和五个核心组成，将开发基于t细胞和抗体治疗的分子和免疫学研究的新方法。该资助的转译研究的一个重要主题是开发淋巴瘤疗法，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，然后将其转化为老年患者群体。一个主要目标是开发针对霍奇金淋巴瘤和CD30+非霍奇金淋巴瘤的基于抗CD30的放射免疫疗法。第二个项目将研究利用工程化cd19特异性t细胞的细胞免疫疗法治疗滤泡性淋巴瘤的有效性。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t细胞的抗原特异性和效应功能定向到淋巴瘤的细胞表面表位。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中发挥作用，第三个项目将对霍奇金淋巴瘤和非霍奇金淋巴瘤患者群体进行纵向研究，以研究预测骨髓发育不良发展的细胞和分子因素，并确定导致骨髓发育不良的事件的分子序列。在第四个项目中，研究人员将开发抗CD20定向治疗的分子工程构建物，以改善CD20+淋巴瘤患者的成像、放射免疫治疗和新型免疫细胞因子治疗。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。本淋巴瘤孢子项目将由五个核心项目提供支持，包括：行政管理、生物统计学和数据管理、用于分子和细胞研究的组织库、生物材料生产和动物模型和实验。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。

DESCRIPTION (provided by applicant): The overall goal of the City of Hope Lymphoma SPORE is to develop translational studies to improve the detection and therapy of Hodgkin's and non-Hodgkin's Lymphoma. This application consisting of four translational research projects and five cores will develop novel approaches that are derived from molecular and immunologic studies of T-cell and antibody-based therapies. An important theme of the translational studies in this grant is to develop lymphoma therapies that will reduce toxicities associated with current treatment regimens for Hodgkin's and non-Hodgkin's Lymphoma which can then be translated to the older patient population. One major goal is to develop anti-CD30 based radioimmunotherapy for both Hodgkin's and CD30+ non-Hodgkin's Lymphoma. A Second Project will study the effectiveness of cellular immunotherapy for follicular lymphoma utilizing engineered 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 T-cells towards cell surface epitopes on lymphomas. Because epidemiologic studies indicate that stem cell damage from pretransplant therapeutic exposures may play a role in the development of myelodysplasia, a Third Project will longitudinally study a population of patients with Hodgkin's and non-Hodgkin's Lymphoma to investigate the cellular and molecular factors that are predictive for development of myelodysplasia, and to determine the molecular sequence of events that lead to myelodysplasia. In a Fourth Project, investigators will develop molecularly engineered constructs for anti-CD20 directed therapeutics to improve imaging, radioimmunotherapy, and novel immunocytokines for the treatment of patients with CD20+ lymphoma. An important component of this project will be to delineate the immunologic effector mechanisms operative in immunocytokine-mediate anti-lymphoma in vivo activity. The projects in this Lymphoma SPORE will be supported by five cores including: Administration, Biostatistics and Data Management, Tissue Bank for molecular and cellular studies, Biological Material Production, and Animal Models and Assays. 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.