Why do CAR T cells cause cytokine release syndrome?

At the same time, these CAR T cells, activated by CAR mediated signals, will proliferate and release a variety of inflammatory factors to trigger a systemic inflammatory response. Therefore, CAR T-cell therapy often produces significant adverse events (AEs), with the most common being cytokine release syndrome (CRS).

What cytokines do CAR T cells release?

CAR T cells alone are capable of producing high concentrations of ICANS-associated cytokines upon antigen stimulation in vitro, including IFNγ, TNF, GM-CSF, IL-6, IL-2, IL-10, IL-13, IL12p70, and IL-8 (112).

What is the role of cytokines in CAR T cell therapy?

Cytokines are pleiotropic hormones involved in multiple processes of immunity, including activation, expansion, differentiation, and migration of immune cells. Both pre-clinical models and clinical trials showed that armoring CAR-T cells with cytokines strengthened the anti-tumor responses of CAR T cells.

What are the hallmark signs of toxicity from CAR T-cell immunotherapy?

Clinical features include: high fever, malaise, fatigue, myalgia, nausea, anorexia, tachycardia/hypotension, capillary leak, cardiac dysfunction, renal impairment, hepatic failure, and disseminated intravascular coagulation.

What occurs in response to cytokine release?

Signs and symptoms of cytokine release syndrome include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Most patients have a mild reaction, but sometimes, the reaction may be severe or life threatening.

What is cytokine release storm?

Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be triggered by various therapies, pathogens, cancers, autoimmune conditions, and monogenic disorders.

What is the most common toxicity with CAR T cell therapy?

The most prominent and well-described toxicity of CAR T cells is cytokine release syndrome (CRS), a constellation of symptoms including fever and hypotension that is caused by cytokines released by the infused T cells.

How is cytokine release syndrome treated?

The current generally accepted sequence of agents to manage severe or life-threatening CRS include: 1) tocilizumab with or without corticosteroids, 2) high-dose corticosteroids if not already employed, and 3) other agents such as siltuximab or multiple tocilizumab doses.

What is the most common toxicity with car T cell therapy?

Does CRS cause neurotoxicity?

The impressive efficacy of CAR T-cells, however, is associated with significant and sometimes life-threatening toxicities, the most prevalent being cytokine release syndrome (CRS) and neurotoxicity (NTX)1,2,3,4.

What does cytokine release cause?

Cytokine release syndrome (CRS) can cause a variety of symptoms, including fever, headaches, and nausea. The symptoms can become severe quickly. CRS occurs when the immune system responds too aggressively to an infection. It can also happen as a result of some types of immunotherapy.

What happens when too many cytokines are released?

These small proteins help control the growth and activity of your blood cells and immune cells. Cytokines tell your immune system to do its job. But when too many cytokines are released, it can cause your immune system to go into overdrive, resulting in cytokine storm.