Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of ex vivo culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.
Highlights
B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the presence of poorly differentiated abnormal B-cell progenitor cells that have a rapid rate of proliferation in the bone marrow [1]
The patient was successfully treated by ssCAR-T-19s and this study proposed that these chimeric antigen receptors (CAR-Ts) might be therapeutically useful in efficiently eradicating infiltrating leukemia cells in the skin and testicle with a mild level of toxicity [70]
As outlined in this review, the unfavorable adverse events of B-ALL CAR-T therapy appear as the leading obstacle in the way of its broader therapeutic benefit; an ideal balance between safety and efficacy is critically required [59]
Summary
B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the presence of poorly differentiated abnormal B-cell progenitor cells that have a rapid rate of proliferation in the bone marrow [1]. The capacity of CD19-redirected CAR-Ts for in vivo activation, expansion, and robust tumoricidal activity, which results in the mentioned high rates of disease remission even in patients with R/R B-ALL, leads to adverse events and toxicities such as cytokine release syndrome (CRS), neurologic toxicities, and Bcell aplasia [14, 24,25,26,27]. Neurologic toxicities can happen following or before CRS onset and it has been evident that its severity correlates with CRS severity [12, 25] Both of these adverse events are important incidences and they may limit the successful clinical outcomes of B-ALL CAR-T therapy [25, 26]. We discuss preclinical and clinical studies that have investigated other factors such as media design, the duration of ex vivo culturing for CAR-T generation, and various phenotype-determining factors that are important for a more efficacious CAR-T therapy in B-ALL and may help achieve better clinical outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
