CAR T cell treatment

CAR T Cell AOP Map

Online access and exploration: https://imsavar.elixir-luxembourg.org
Development status: First version is complete and published
Disease treated: Cancer
Sustainable support: LCSB, MINERVA Platform
Construction tool: CellDesigner
Funding: IMI2 imSAVAR No 853988, https://imsavar.eu
License: Creative Commons Attribution 4.0 International (CC BY 4.0) License
Publication: Preprint
Contact: Alexander Mazein, University of Luxembourg, alexander.mazein(at)uni.lu

Description

Chimeric antigen receptor (CAR), or chimeric T cell receptor, is an artificial T cell receptor protein engineered to give T cells an ability to target a specific antigen. This receptor type is named chimeric because it combines antigen-binding and T-cell-activating functions. CAR T cell therapy is a form of immunotherapy for treating cancer. Cytokine release syndrome (CRS) is the most common type of toxicity caused by CAR T cell therapy.

In toxicology, an adverse outcome pathway (AOP), or in immunotoxicology - an immune-related adverse outcome pathway (irAOP), is a concept that is used to visualise and study adverse effects of treatments. An irAOP includes a molecular initiating event (MIE), key events (KEs), key event relationships (KERs) and an adverse outcome (AO). KEs are defined by connecting physiological events to test systems and measurable clinical parameters.

In this project, we use a pre-developed irAOP of CRS induced by CAR T cell treatment to build a detailed description of adverse outcome mechanisms. This is done by combining the AOP approach with the disease map approach and focusing on relevant cytokines, receptors and cell types, as well as on connections between them.

Funding

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853988.