Optimization of mononuclear cell collection material for chimeric antigen receptor T-cell therapy manufacturing: a narrative review

Zhou, Yi Yuan; Maitta, Robert W.*

University Hospitals Cleveland Medical Center and Case Western Reserve University Sch

ool of Medicine, Cleveland, OH, USA

*Correspondence to: Robert W. Maitta, MD, PhD, robert.maitta@case.edu.

Abstract

The collection of mononuclear cells via apheresis, although routinely performed across the world, requires a great deal of training and expertise to be successful. Chimeric antigen receptor T-cell (CAR-T) therapy has become a highly researched area for the exploration of new effective therapies against hematologic malignancies while defining the latest technological advances in targeted cancer-specific immune regeneration. Importantly, CAR-T-cell therapy has been shown to be effective in difficult-to-treat and refractory cancers. Since the currently available CAR-T-cell therapies are directed at treating relapsed/refractory hematological malignancies, the collection of potent and qualitatively superior autologous T cells from patients at sufficient quantities for CAR-T-cell manufacturing is challenging and may represent the most crucial factor determining manufacturing failure. Furthermore, allogeneic T cells may be used in the near future as sources to produce potent CAR-T-cell therapies. In this review, we look at factors that influence T-cell quantity and quality, strategies to improve mononuclear cell collection, cryopreservation, patient optimization, and possible future sources of T cells to derive a better T-cell starting product that favors the success of CAR-T-cell manufacturing.

嵌合抗原受体 T 细胞疗法和癌症特异性免疫反应再生相关单核细胞收集材料的优化：叙述性综述

摘要

通过无细胞抽吸术采集单核细胞虽然在全世界范围内都是常规操作，但要取得成功需要大量的培训和专业知识。嵌合抗原受体 T 细胞（CAR-T）疗法已成为探索血液系统恶性肿瘤新有效疗法的高度研究领域，同时也确定了癌症特异性靶向免疫再生的最新技术进展。重要的是，CAR-T疗法已被证明对难以治疗和难治性癌症有效。由于目前可用的 CAR-T 疗法都是针对治疗复发/难治性血液恶性肿瘤的，因此从患者身上收集足够数量的强效、质量上乘的自体 T 细胞用于 CAR-T 生产是一项挑战，可能是决定生产失败的最关键因素。此外，异体 T 细胞有可能在不久的将来被用作生产强效 CAR-T 疗法的来源。此综述探讨了影响 T 细胞数量和质量的因素、改善单核细胞采集的策略、冷冻保存、患者优化以及未来可能的 T 细胞来源，以获得更好的 T 细胞起始产品，促进 CAR-T 生产的成功。