Multicenter Study Using IMC to Analyze the Impact of ICANS on Microglia
- Conditions
- CAR T-Cell-Related Encephalopathy SyndromeICANS, Grade Unspecified
- Registration Number
- NCT05811117
- Lead Sponsor
- University of Freiburg
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 8
- Patients that had developed ICANS
- CAR T cell infusion for lymphoid malignancy (NHL or ALL)
- Lack of consent of patient or legal guardian
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method HLA-DRA and HLA-DR on Iba1+ cells 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 2 years Clusters of activated microglia and macrophages will be studied in patients with ICANS
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Freiburg University Medical Center
🇩🇪Freiburg, Baden Württemberg, Germany