CAR T-Cell-Related Encephalopathy Syndrome, ICANS, Grade Unspecified
Conditions
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.
Interventions
DIAGNOSTIC_TESTThere 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.
Sponsors
University of Freiburg
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany
Outcome results
None listed