City of Hope Lymphoma SPORE

描述(由申请者提供)：希望之城淋巴瘤孢子的总体目标是开发翻译研究，以改进霍奇金淋巴瘤和非霍奇金淋巴瘤的检测和治疗。这项申请由四个翻译研究项目和五个核心组成，将开发源于T细胞和抗体治疗的分子和免疫学研究的新方法。这笔赠款中的翻译研究的一个重要主题是开发淋巴瘤疗法，以减少与目前霍奇金淋巴瘤和非霍奇金淋巴瘤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+非霍奇金淋巴瘤的抗CD30放射免疫疗法。第二个项目将研究利用工程CD19特异性T细胞对滤泡性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T细胞的抗原特异性和效应功能重定向于淋巴瘤的细胞表面表位。由于流行病学研究表明，移植前暴露的治疗对干细胞的损伤可能在骨髓发育不良的发展中起作用，第三个项目将对霍奇金淋巴瘤和非霍奇金淋巴瘤患者进行纵向研究，以调查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，研究人员将为抗CD20定向治疗开发分子工程构建物，以改进成像、放射免疫治疗和用于CD20+淋巴瘤患者治疗的新型免疫细胞因子。该项目的一个重要组成部分将是描述在体内免疫细胞因子介导的抗淋巴瘤活性中起作用的免疫效应机制。这个淋巴瘤孢子的项目将得到五个核心的支持，包括：行政管理、生物统计和数据管理、用于分子和细胞研究的组织银行、生物材料生产以及动物模型和分析。该淋巴瘤孢子还将支持发展研究计划和职业发展计划，以促进专注于淋巴瘤的试验性翻译研究项目和年轻研究人员的进步。

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.