采用嵌合抗原受体（CAR-T）细胞成功治疗B细胞恶性肿瘤患者是采用细胞免疫治疗（ACT）领域的一个突破。然而，CAR-T疗法并不适用于所有患者，而且还存在一些需求尚未满足。特别是，CAR-T细胞的生产成本高、劳动密集且具有后勤挑战；此外，CAR-T细胞输注所导致的毒性反应，如细胞因子释放综合征（CRS）和免疫效应细胞相关的神经毒性综合征（ICANS），已经得到广泛的记录。Cytokine-induced killer（CIK）细胞等替代的细胞治疗产品有望克服其中部分障碍。CIK细胞是一种异质性的多克隆CD3+CD56+ T细胞，具有NK细胞的表型和功能特性。CIK细胞的细胞毒性是通过与天然杀伤类2成员D（NKG2D）分子的结合在一个重要的组织相容性复合物（MHC）无限制的方式下发挥作用，针对广泛的血液和实体瘤、而无需先前抗原暴露或预激活。CIK细胞的主要潜力在于在异基因移植环境中引起移植物抗宿主病（GvHD）反应的能力非常有限。CIK细胞通过一种简单且非常高效的扩增方案进行生产，该方案导致效应细胞大规模扩增，与CAR-T细胞相比需要更低的财务投入。实际上，CAR-T制造需要使用昂贵的GMP级病毒载体进行工程改造，并在集中制造设施中进行，而CIK细胞的生产则在当地的学术GMP设施中成功进行，CIK细胞治疗在许多国家已经获得执照。此外，与CAR-T细胞相比，在经过CIK细胞治疗的患者中观察到的毒性反应减少了，因此进一步减少了与住院和输注后监测患者相关的成本，从而鼓励在门诊环境中进行细胞治疗的交付。本综述旨在概述CAR-T细胞疗法的局限性，并说明利用CIK细胞的独特特性如何克服这些缺点。我们强调使用CIK细胞作为治疗产品的无可否认的优势，突出了进一步研究该主题的机会。版权所有 © 2023 Cappuzzello, Vigolo, D’Accardio, Astori, Rosato and Sommaggio.

The successful treatment of patients affected by B-cell malignancies with Chimeric Antigen Receptor (CAR)-T cells represented a breakthrough in the field of adoptive cell therapy (ACT). However, CAR-T therapy is not an option for every patient, and several needs remain unmet. In particular, the production of CAR-T cells is expensive, labor-intensive and logistically challenging; additionally, the toxicities deriving from CAR-T cells infusion, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), have been documented extensively. Alternative cellular therapy products such as Cytokine-induced killer (CIK) cells have the potential to overcome some of these obstacles. CIK cells are a heterogeneous population of polyclonal CD3+CD56+ T cells with phenotypic and functional properties of NK cells. CIK cell cytotoxicity is exerted in a major histocompatibility complex (MHC)-unrestricted manner through the engagement of natural killer group 2 member D (NKG2D) molecules, against a wide range of hematological and solid tumors without the need for prior antigen exposure or priming. The foremost potential of CIK cells lies in the very limited ability to induce graft-versus-host disease (GvHD) reactions in the allogeneic setting. CIK cells are produced with a simple and extremely efficient expansion protocol, which leads to a massive expansion of effector cells and requires a lower financial commitment compared to CAR-T cells. Indeed, CAR-T manufacturing involves the engineering with expensive GMP-grade viral vectors in centralized manufacturing facilities, whereas CIK cell production is successfully performed in local academic GMP facilities, and CIK cell treatment is now licensed in many countries. Moreover, the toxicities observed for CAR-T cells are not present in CIK cell-treated patients, thus further reducing the costs associated with hospitalization and post-infusion monitoring of patients, and ultimately encouraging the delivery of cell therapies in the outpatient setting. This review aims to give an overview of the limitations of CAR-T cell therapy and outline how the use of CIK cells could overcome such drawbacks thanks to their unique features. We highlight the undeniable advantages of using CIK cells as a therapeutic product, underlying the opportunity for further research on the topic.Copyright © 2023 Cappuzzello, Vigolo, D’Accardio, Astori, Rosato and Sommaggio.