Cytokine release syndrome

Question 1

What is CRS?

Answer 1

Cytokine Release Syndrome is a (severe) systemic inflammatory response that is triggered by infections or certain drugs.
CRS can arise after infusion of several antibody-based therapies, following administration of non-protein-based cancer drugs, after haploidentical donor stem cell transplantation (graft-versus-host disease) or after T cell engaging immunotherapy (like CAR T-cell therapy).
T cell engaging cancer immunotherapies carry a particularly high risk of CRS.

Question 2

What happens in CRS?

Answer 2

Activation of mainly T cells or lysis of immune cells induces a release of IFN-γ or TNF-α. This leads to the activation of macrophages, dendritic cells, other immune cells, and endothelial cells. These cells further release proinflammatory cytokines. Importantly, macrophages and endothelial cells produce large amounts of IL-6. IL-6 in a positive feedback loop manner activates T cells and other immune cells leading to a cytokine storm.

Question 3

What treatment is used for preventing CRS?

Answer 3

Tocilizumab is an anti-IL6 therapy which prevents CRS without affecting anti-tumor activity of bispecific antibodies.