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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion. | Diagnostic Test | We will study patients that undergo autopsy after CAR T cell infusion. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Patients that had developed ICANS after CAR T cell infusion will be analyzed.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Freiburg University Medical Center | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34260836 | Result | Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122. |
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