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

University of Freiburg

Status: Completed

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

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

Study type: Observational

Funder types: Other

Identifiers

NCT05811117

UKLFR02022021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Volunteers: No Healthy Volunteers

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