Modeling Risk for Hypogammaglobulinemia, Infections, and Mortality with Chimeric Antigen Receptor (CAR) T-cell Therapy

使用嵌合抗原受体 (CAR) T 细胞疗法模拟低丙种球蛋白血症、感染和死亡的风险

基本信息

  • 批准号:
    10445348
  • 负责人:
  • 金额:
    $ 19.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-06-24 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY: This proposal details a five-year research training program that will allow Sara Barmettler, MD to achieve her goal of becoming an independent clinical researcher focused on improving outcomes among patients with primary and secondary immunodeficiency. Dr. Barmettler is an Instructor in Medicine at Harvard Medical School (HMS) and Assistant in Medicine in Allergy-Immunology at Massachusetts General Hospital (MGH) who has demonstrated academic productivity and a strong commitment to clinical research. Her prior training and research in immune deficiency and investigating immunologic outcomes in other B-cell targeted therapies (including the largest cohort to date of rituximab-treated patients), have established the skills and experience critical for achieving her proposed research aims. The research proposal will advance our understanding of immunologic risk factors for infections, morbidity, mortality, and decreased quality of life after chimeric antigen receptor (CAR) T-cell therapy. Aim 1 utilizes a large retrospective cohort of patients to determine the immunologic impact and clinical significance of hypogammaglobulinemia following CAR T-cell therapy. Regression models and Bayesian network analysis will be used to define risk factors for development of infections and poor outcomes and to develop a clinical risk prediction model. Aim 2 will evaluate the impact of hypogammaglobulinemia and immunoglobulin replacement on morbidity, mortality, and quality of life and evaluate cost-effectiveness of early intervention. In accomplishing these aims, Dr. Barmettler will address critical gaps in our knowledge of immune dysregulation following the use of CAR T-cell therapy with the ultimate goal of improving patient outcomes. Dr. Barmettler will perform this work under the mentorship of Professor Carlos Camargo, an internationally recognized expert in clinical epidemiology with an outstanding track record of mentorship. Dr. Barmettler has assembled a team of mentors and collaborators with expertise in epidemiology, biostatistics, B- cell immunology, CAR T-cell therapy, and infectious disease, whose support will contribute to the success of this project. In the exceptional training environment at MGH and HMS, Dr. Barmettler will complete coursework and training in advanced biostatistical techniques and epidemiology, leadership, and responsible conduct of research. The training and mentoring plans outlined in this Career Development proposal, along with the outstanding collaborative opportunities and intellectual environment at MGH and HMS, will allow Dr. Barmettler to achieve the research and educational aims and to, thereby, establish herself as an independent physician- scientist with expertise in advanced biostatistical techniques and mechanisms of immune deficiency.
项目概要: 该提案详细说明了一个为期五年的研究培训计划,将允许萨拉巴梅特勒,医学博士实现她的 目标是成为一名独立的临床研究人员,专注于改善患者的预后, 原发性和继发性免疫缺陷。Barmettler博士是哈佛医学院的医学讲师 (HMS)以及马萨诸塞州总医院(MGH)过敏免疫学医学助理, 表现出学术生产力和对临床研究的坚定承诺。她之前的训练和 免疫缺陷研究和其他B细胞靶向治疗的免疫学结果研究 (包括迄今为止最大的利妥昔单抗治疗患者队列),已经建立了技能和经验, 这对实现她提出的研究目标至关重要。 这项研究计划将促进我们对感染的免疫风险因素的理解, 嵌合抗原受体(CAR)T细胞治疗后的发病率、死亡率和生活质量下降。要求1 利用一个大型的回顾性患者队列来确定免疫学影响和临床意义, CAR T细胞治疗后的低丙种球蛋白血症。回归模型和贝叶斯网络分析将 用于定义发生感染和不良结局的风险因素, 预测模型目的2将评估低丙种球蛋白血症和免疫球蛋白替代的影响 对发病率、死亡率和生活质量的影响,并评估早期干预的成本效益。在完成 为了实现这些目标,Barmettler博士将解决我们对免疫失调的认识中的关键空白, CAR T细胞疗法的最终目标是改善患者的预后。 Barmettler博士将在卡洛斯卡马戈教授的指导下进行这项工作, 国际公认的临床流行病学专家,具有出色的指导记录。博士 Barmettler组建了一个由流行病学、生物统计学、B- 细胞免疫学,CAR T细胞疗法和传染病,他们的支持将有助于这一研究的成功。 项目在MGH和HMS的特殊培训环境中,Barmettler博士将完成课程, 在先进的生物统计技术和流行病学,领导和负责任的研究行为的培训。 本职业发展建议书中概述的培训和指导计划,以及沿着 杰出的合作机会和MGH和HMS的智力环境,将使Barmettler博士 实现研究和教育目标,从而成为一名独立的医生- 在先进的生物统计技术和免疫缺陷机制方面拥有专业知识的科学家。

项目成果

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Sara Barmettler其他文献

Sara Barmettler的其他文献

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{{ truncateString('Sara Barmettler', 18)}}的其他基金

Modeling Risk for Hypogammaglobulinemia, Infections, and Mortality with Chimeric Antigen Receptor (CAR) T-cell Therapy
使用嵌合抗原受体 (CAR) T 细胞疗法模拟低丙种球蛋白血症、感染和死亡的风险
  • 批准号:
    10621771
  • 财政年份:
    2021
  • 资助金额:
    $ 19.66万
  • 项目类别:
Modeling Risk for Hypogammaglobulinemia, Infections, and Mortality with Chimeric Antigen Receptor (CAR) T-cell Therapy
使用嵌合抗原受体 (CAR) T 细胞疗法模拟低丙种球蛋白血症、感染和死亡的风险
  • 批准号:
    10284394
  • 财政年份:
    2021
  • 资助金额:
    $ 19.66万
  • 项目类别:
Modeling Risk for Hypogammaglobulinemia, Infections, and Mortality with Chimeric Antigen Receptor (CAR) T-cell Therapy
使用嵌合抗原受体 (CAR) T 细胞疗法模拟低丙种球蛋白血症、感染和死亡的风险
  • 批准号:
    10487663
  • 财政年份:
    2021
  • 资助金额:
    $ 19.66万
  • 项目类别:

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