Recombinant IL-2 treatment

IL-2 AOP Map

Development status: Active development
Diseases treated: Cancer, autoimmune diseases
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: Manuscript in preparation
Contact: Alexander Mazein, University of Luxembourg, alexander.mazein(at)uni.lu

Description

Recombinant interleukin-2 (IL-2) is a therapeutic used to treat cancer and autoimmunity. Higher dosages can lead to systemic toxicities that are manifested by skin rash, hepatotoxicity and vascular leakage. These three adverse outcomes (AOs) are described by three adverse outcome pathways (AOPs).

An adverse outcome pathway (AOP), or 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 irAOPs developed by the imSAVAR experts for skin rash, hepatotoxicity and vascular leakage induced by recombinant IL-2. On the basis of these irAOPs we build detailed descriptions of adverse outcome mechanisms. For that we combine 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.