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发展转化研究，以提高霍奇金淋巴瘤和非霍奇金淋巴瘤的检测和治疗。 该申请包括四个转化研究项目和五个核心，将开发来自T细胞和抗体疗法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人群。 一个主要目标是开发基于抗CD30的放射免疫疗法用于霍奇金淋巴瘤和CD30+非霍奇金淋巴瘤。第二个项目将研究细胞免疫疗法的有效性滤泡性淋巴瘤利用工程CD19特异性T细胞。 该项目的研究人员开发了一种T细胞遗传修饰平台，用于表达嵌合免疫受体，将T细胞的抗原特异性和效应子功能重定向到淋巴瘤上的细胞表面表位。 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骨髓增生异常的发展中发挥作用，第三个项目将纵向研究霍奇金淋巴瘤和非霍奇金淋巴瘤患者的人群，以调查预测骨髓增生异常发展的细胞和分子因素，并确定导致骨髓增生异常的事件的分子序列。 在第四个项目中，研究人员将开发用于抗CD20定向治疗的分子工程构建体，以改善成像，放射免疫治疗和新型免疫细胞因子用于治疗CD20+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。在这个淋巴瘤孢子的项目将由五个核心支持，包括：管理，生物统计学和数据管理，组织库的分子和细胞研究，生物材料生产，动物模型和检测。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。

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.