The biological basis and clinical symptoms of CAR-T therapy-associated toxicites

Currently, immunotherapy is attracting a lot of attention and may potentially become a leading approach in the treatment of cancer. One emerging therapeutic, the chimeric-antigen receptor T-cell adoptive immunotherapy (CAR-T) is showing remarkable efficacy in the treatment of several B-cell malignancies. The popularity of CAR-T has been founded on two CAR T-cell products recently approved by FDA (during 2017) in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia and B-cell lymphoma. However, their toxicities observed in clinical trials were extremely significant and in some cases even fatal with no approved algorithms for toxicity prediction being available to date. A deeper understanding of the biological basis of such complications is the key to prompt and comprehensive clinical management. Here we review the wide spectrum of effects associated with CAR T cell therapy with a major focus on the pathogenesis of cytokine release syndrome and neurotoxicity as the most common, potentially life-threatening effects of this treatment. We discuss the basis of clinical management and the existing models that predict the severity of toxicity, as well as the key factors that modulate this event. Finally, we will summarize the literature detailing universal allogenic CAR T-cells and their toxicity profile.