Multicenter Study Using IMC to Analyze the Impact of ICANS on Microglia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia

Conditions
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ICANS, Grade Unspecified, CAR T-Cell-Related Encephalopathy Syndrome

Intervention / Treatment
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* Diagnostic Test: There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients that had developed ICANS CAR T cell infusion for lymphoid malignancy (NHL or ALL) Exclusion Criteria: Lack of consent of patient or legal guardian
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.|We will study patients that undergo autopsy after CAR T cell infusion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HLA-DRA and HLA-DR on Iba1+ cells | We will study HLA-DRA and HLA-DR on Iba1+ cells | 2 years | 
| Clusters of activated microglia and macrophages will be studied in patients with ICANS | Clusters of activated microglia and macrophages will be studied in patients with ICANS | 2 years |