Axicabtagene

Axicabtagene ciloleucel, commonly abbreviated axi-cel and marketed as Yescarta, is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy. It uses autologous T cells collected from the patient, genetically modified to express a CAR that recognizes CD19 on B cells, expanded, and infused back after lymphodepleting chemotherapy. The CAR includes a CD28 co-stimulatory domain, which drives T-cell activation and targeted cytotoxicity against CD19-positive B cells.

Production and administration: T cells are obtained by leukapheresis, engineered in centralized facilities, and returned as a single infusion following a short lymphodepleting regimen, typically with cyclophosphamide and fludarabine. Treatment is delivered in specialized centers with close post-infusion monitoring due to risks of immune-mediated toxicity.

Clinical use: In the United States, axi-cel is approved for adults with certain relapsed or refractory B-cell malignancies after prior systemic therapy, most notably large B-cell lymphoma. Regulatory approvals in other regions have extended indications to include additional CD19-positive diseases such as primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and some cases of follicular lymphoma, with specifics varying by jurisdiction.

Safety and history: The most common adverse events are cytokine release syndrome and neurotoxicity (immune effector cell-associated neurotoxicity syndrome), along with cytopenias and infections. Management may require hospitalization and targeted therapies such as tocilizumab and corticosteroids. Axicabtagene ciloleucel was developed by Kite Pharma with the University of Pennsylvania and received FDA approval in 2017, marking a notable advance in CAR-T therapy for B-cell cancers.