Understanding Inflammatory Arthritis due to Immune Checkpoint Inhibitors

了解免疫检查点抑制剂引起的炎症性关节炎

基本信息

批准号：
10224867
负责人：
Laura Christine Cappelli
金额：
$ 15.58万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-16 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224867
关键词：
Address Adrenal Cortex Hormones Alleles Antibodies Area Arthritis Autoantibodies Autoimmune Autoimmune Diseases Award Biological Assay Characteristics Clinical Clinical Data Clinical Investigator Collaborations Collection Data Data Science Degenerative polyarthritis Development Diagnosis Disease Dose Epitopes Evaluation Event Family history of Fostering Foundations Future Goals Health Immune Immune checkpoint inhibitor Immunogenetics Immunologic Factors Immunosuppression Immunotherapy Inflammatory Arthritis Institutes Interleukin-17 Interleukin-6 Joints Knowledge Laboratories Literature Machine Learning Malignant Neoplasms Mentors Methods Modeling Monitor Morbidity - disease rate Myositis Oncology Operative Surgical Procedures Pathogenesis Pathogenicity Pathway interactions Patients Phenotype Predictive Factor Prognosis Public Health Schools Research Research Personnel Resolution Resources Rheumatism Rheumatoid Arthritis Rheumatology Risk Risk Factors Science Serum Sjogren&apos s Syndrome Specialist Subgroup Surveys Sushi Domain Syndrome T-Lymphocyte Techniques Time Trauma Treatment Protocols Vasculitis Visit active method anti-PD-1 anti-tumor immune response cancer immunotherapy cancer therapy career development checkpoint therapy clinical heterogeneity clinical phenotype clinical risk clinically relevant cohort cytokine data standards experimental study human leukocyte antigen testing immune-related adverse events improved insight meetings negative affect patient stratification potential biomarker prospective response rheumatologist risk stratification skills symposium targeted treatment therapeutic target translational scientist tumor tumor immunology

项目摘要

Project Summary/Abstract The major goals of this proposal are to attain skills required to be an independent clinical and translational researcher in rheumatology and to enhance understanding of a new rheumatic disease, inflammatory arthritis (IA) due to immune checkpoint inhibitors (ICIs). ICIs are revolutionizing cancer treatment but also cause immune related adverse events. ICI-induced IA is the immune related adverse event most likely to be encountered by rheumatologists. ICI-induced IA causes significant morbidity, is clinically heterogeneous, and can persist after ICI cessation. The proposed project will utilize a group of well characterized patients with ICI- induced IA and ICI-treated control patients who do not develop IA to address several important questions. First, the clinical heterogeneity within ICI-induced IA will be evaluated and factors that predict persistence of IA beyond cessation of ICI therapy will be established. Next, clinical and immunogenetic risk factors for developing ICI-induced IA will be determined. Finally, serum cytokine profiles and autoantibodies before and after ICI treatment will be compared in patients with ICI-induced IA and control patients who are treated with ICIs and do not develop IA. These experiments will address key knowledge gaps for this emerging clinical entity. Specifically, defining relevant clinical subgroups will allow for differential monitoring and treatment of patients. Understanding risk factors for development of IA will allow for risk stratification of patients prior to therapy. Cytokines that are elevated in ICI-induced IA patient sera could serve as future therapeutic targets. Finally, understanding presence of autoantibodies and when they develop in the course of ICI treatment will give insight into pathogenesis and identify potential biomarkers. Concurrently with conducting research during the proposal, the candidate will participate in a variety of career development activities taking advantage of the rich resources of Johns Hopkins in the Division of Rheumatology, the Bloomberg Kimmel Institute for Cancer Immunotherapy, and the Bloomberg School of Public Health. The candidate will participate in didactic coursework, conferences, and mentoring meetings with a diverse group of mentors from rheumatology, oncology, laboratory science, and data science. At the end of this award, the candidate will be an independent clinical investigator in the area of cancer immunotherapy and autoimmune disease and will establish a multi- center consortium with standardized data and biospecimen collection for rheumatic irAEs and for patients with preexisting autoimmune disease who are treated with ICIs.

项目摘要/摘要该提案的主要目标是获得独立临床和翻译所需的技能风湿病学研究人员，并增强对新风湿性疾病的理解（IA）由于免疫检查点抑制剂（ICI）。 ICI正在彻底改变癌症治疗，但也会导致免疫相关的不良事件。 ICI引起的IA是免疫相关的不良事件风湿病学家遇到。 ICI诱导的IA引起明显的发病率，在临床上是异质的，并且 ICI停止后可以持续。拟议的项目将利用一组具有良好特征的ICI的患者诱导的IA和ICI治疗的对照患者，他们不开发IA来解决几个重要问题。首先，将评估ICI诱导的IA内的临床异质性，并预测IA的持续性因素除了停止ICI疗法之外，还将确定。接下来，临床和免疫遗传危险因素将确定开发ICI引起的IA。最后，血清细胞因子特征和自身抗体在ICI诱导的IA和对照患者接受治疗的患者中，将比较ICI治疗后 ICI，不发展IA。这些实验将解决此新兴临床的关键知识差距实体。具体而言，定义相关的临床子组将允许对患者。了解IA发展的风险因素将允许在患者之前进行风险分层治疗。 ICI诱导的IA患者血清中升高的细胞因子可以用作将来的治疗靶因子。最后，了解自身抗体的存在以及在ICI治疗过程中发展时深入了解发病机理并识别潜在的生物标志物。同时与进行研究提案，候选人将利用各种职业发展活动约翰·霍普金斯（Johns Hopkins）的丰富资源在风湿病学系，彭博金梅尔癌症研究所免疫疗法和彭博公共卫生学院。候选人将参加教学课程，会议和指导会议与风湿病学的一群导师，肿瘤学，实验室科学和数据科学。在该奖项结束时，候选人将是独立的癌症免疫疗法和自身免疫性疾病领域的临床研究者，将建立多种多样的中心财团，标准化数据和风湿性伊拉斯的生物测量收集以及患者先前有ICI治疗的自身免疫性疾病。