In this review we discuss some of the mechanistic contributions intrinsic to the CAR-T construct, the tumor being treated, and the individual patient that impact the development and severity of CRS and neurotoxicity.
Specific toxicities related to CAR-T like Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) could be fatal and need close monitoring and prompt treatment to avoid mortality and improve efficacy of the treatment.
Cytokine release syndrome (CRS) and CAR-T-associated encephalopathy syndrome (neurotoxicity) are the most common adverse effects associated with CAR-T therapy.
T cell-based therapies (blinatumomab and CAR T cell therapy) have produced unprecedented responses in relapsed and refractory (r/r) acute lymphoblastic leukemia (ALL) but is accompanied with significant toxicities, of which one of the most common and serious is cytokine release syndrome (CRS).
Of note, we also found that the genetic inactivation of GMCSF does not impair the antitumor function or proliferative capacity of CAR T-cells <i>in vitro</i> We conclude that it is possible to prevent CRS by using "all-in-one" GMCSF-knockout CAR T-cells.
Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma.
A logistic model was used to analyze the association of severe CRS incidence with CAR-T dose and baseline factors including age and baseline tumor burden.
Current research suggests that patients with a higher disease burden and higher CAR-T cell doses are positively associated with the development of ICANS, as are elevated serum levels of proinflammatory cytokines and the presence of cytokine release syndrome (CRS).
Clinical experience with the anti-CD19 CAR T cell therapy tisagenlecleucel at the University of Pennsylvania (Penn) was used to develop the Penn grading scale for CRS.
In the clinic, chimeric antigen receptor-modified T (CAR T) cell therapy is frequently associated with life-threatening cytokine-release syndrome (CRS) and neurotoxicity.