An explorable model of an adverse outcome pathway of cytokine release syndrome related to the administration of immunomodulatory biotherapeutics and cellular therapies

INTRODUCTION: Cytokine release syndrome (CRS) is a potentially severe systemic inflammatory condition triggered by various immunomodulatory therapies, making understanding its pathogenesis critical for improving patient outcomes. RESULTS/METHODS: By combining immunotoxicology and systems biology approaches, we offer a novel and integrative conceptual model of CRS as an adverse outcome (AO), induced by five different immunomodulatory biotherapies: 1) chimeric antigen receptor (CAR) T cells, 2) checkpoint inhibitors, 3) T cell engaging bispecific modalities, 4) monoclonal antibodies targeting and activating T cell receptors, and 5) Fc

• Mazein, A.
• Lopata, O.
• Reiche, K.
• Sewald, K.
• Alb, M.
• Sakellariou, C.
• Gogesch, P.
• Morgan, H.
• Neuhaus, V.
• Pham, N. N.
• Sommer, C.
• Perkins, E.
• Fogal, B.
• Shoaib, M.
• Schneider, R.
• Satagopam, V.
• Ostaszewski, M.