Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing

Chimeric antigen receptor (CAR) T-cell therapy is an individualized immunotherapy that genetically repro-grams a patient's T cells to target and eliminate cancer cells. Tisagenlecleucel is a US Food and Drug Adminis-tration-approved CD19-directed CAR T-cell therapy for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia and r/r diffuse large B-cell lymphoma. Manufacturing CART cells is an intricate pro-cess that begins with leukapheresis to obtain T cells from the patient's peripheral blood. An optimal leuka-pheresis product is essential to the success of CAR T-cell therapy; therefore, understanding factors that may affect the quality or T-cell content is imperative. CAR T-cell therapy requires detailed organization through-out the entire multistep process, including appropriate training of a multidisciplinary team in leukapheresis collection, cell processing, timing and coordination with manufacturing and administration to achieve suit-able patient care. Consideration of logistical parameters, including leukapheresis timing, location and patient availability, when clinically evaluating the patient and the trajectory of their disease progression must be reflected in the overall collection strategy. Challenges of obtaining optimal leukapheresis product for CAR T -cell manufacturing include vascular access for smaller patients, achieving sufficient T-cell yield, eliminating contaminating cell types in the leukapheresis product, determining appropriate washout periods for medica-tion and managing adverse events at collection. In this review, the authors provide recommendations on navigating CAR T-cell therapy and leukapheresis based on experience and data from tisagenlecleucel manufacturing in clinical trials and the real-world setting.(c) 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Chimeric antigen receptor (CAR) T-cell therapy is an individualized immunotherapy that targets and eliminates cancer cells by genetically reprogramming a patient's T cells. The manufacturing process for CART cells is complex, and optimal leukapheresis product is crucial for the success of CAR T-cell therapy.