Review article: CAR-T Immunotherapy Limitations and Advancements for Relapse and Refractory Pediatric B-Cell Malignancies
Diana Woller, Brenda Barnes, Joel E. Mortensen
Abstract
Chimeric antigen receptors (CARs) are genetically engineered, T-lymphocyte receptors that target hematological cancer cells and solid tumors. CAR-T cell immunotherapies for B-Cell malignancies target CD19 positive cells and have shown dramatic results in treating pediatric patients since becoming licensed as tisa¬genlecleucel by the US Food and Drug Administration in 2018. Tisagenlecleucel is used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) and large diffuse B-cell lymphomas (DLBCL) in children and young adults up to age 25. While CAR-T immunotherapies have shown continued promise, crucial limitations are being investigated to improve anti-CD19 CAR-T toxicity, off-target events, bridging and dual treatment requirements, and manufacturing capabilities. This review examines the current limitations and advancements of anti-CD19 CAR-T immunotherapy for pediatric B-cell malignancies focusing on relevant improve¬ment strategies for engineering, efficacy, and patient safety.
Key words: Anti-CD19 CAR-T cells; pediatric acute lymphoblastic leukemia; pediatric diffuse large B-cell lymphoma; replapsed/refractory B-cell malignancies; limitations of Anti-CD19CAR-T cell therapy; anti-CD19 CAR-T manufacturing advancements; cytokine release syndrome; neurotoxicity; immunotherapy
Int. J. Bio. Lab. Sci 2022(11)2:80-89 【PDF】