Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- HLA-DRA and HLA-DR on Iba1+ cells
研究概览
简要总结
Immunotherapy with chimeric antigen receptor (CAR) T cell therapy can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. In this study, the investigators plan to examine the role of microglia as the primary parenchymal immune cells of the central nervous system (CNS) during ICANS in human samples. The samples will be analyzed using imaging-mass-cytometry-based analysis (IMC). Single-cell data will be obtained through machine learning supervised segmentation of IMC data. Single-cell marker expression in all cells and in microglia (Iba1+ cells) will be analyzed in patients with ICANS.
详细描述
Immunotherapy with chimeric antigen receptor (CAR) T cell therapy can cause immune effector cell-associated neurotoxicity syndrome (ICANS).
Previous studies have shown a role for IL-1beta and IL-6 in xenograft mouse models.
However, the molecular mechanisms leading to ICANS are not well understood. In this study, the investigators plan to examine the role of microglia as the primary parenchymal immune cells of the central nervous system (CNS) during ICANS in human samples. The samples will be analyzed using imaging-mass-cytometry-based analysis (IMC). Single-cell data will be obtained through machine learning supervised segmentation of IMC data. Single-cell marker expression in all cells and in microglia (Iba1+ cells) will be analyzed in patients with ICANS. The participants are patients treated with chimeric antigen receptor (CAR) T cell therapy. The patients will received TSPO-PET imaging if available and if an autopsy is performed underroutine conditions tissue is collected for IMC based analysis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients that had developed ICANS
- •CAR T cell infusion for lymphoid malignancy (NHL or ALL)
排除标准
- •Lack of consent of patient or legal guardian
结局指标
主要结局
HLA-DRA and HLA-DR on Iba1+ cells
时间窗: 2 years
We will study HLA-DRA and HLA-DR on Iba1+ cells
Clusters of activated microglia and macrophages will be studied in patients with ICANS
时间窗: 2 years
Clusters of activated microglia and macrophages will be studied in patients with ICANS
次要结局
未报告次要终点
研究者
Robert Zeiser
Director Division of Tumor Immunology
University of Freiburg