Document Type

Article

Publication Date

9-2022

Identifier

DOI: 10.1016/j.jcyt.2022.05.003

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is an individualized immunotherapy that genetically reprograms a patient's T cells to target and eliminate cancer cells. Tisagenlecleucel is a US Food and Drug Administration-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 CAR T cells is an intricate process that begins with leukapheresis to obtain T cells from the patient's peripheral blood. An optimal leukapheresis 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 throughout 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 suitable 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 medication 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.

Journal Title

Cytotherapy

Volume

24

Issue

9

First Page

869

Last Page

878

MeSH Keywords

Antigens, CD19; Humans; Immunotherapy, Adoptive; Leukapheresis; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; T-Lymphocytes

Keywords

acute lymphoblastic leukemia; algorithm; chimeric antigen receptor T cells; diffuse large B-cell lymphoma; leukapheresis; recommendations

Comments

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Link: https://www.isct-cytotherapy.org/article/S1465-3249(22)00641-7/fulltext

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