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用于癌症免疫治疗的工程化嵌合抗原受体自然杀伤细胞:基于慢病毒的NK-92细胞嵌合抗原受体转导

Engineered CAR-NK Cells for Cancer Immunotherapy: Lentiviral-Based CAR Transduction of NK-92 Cells.

作者信息

Schmidt Dayane, Tirapelle Mariane Cariati, Ebrahimabadi Sima, Biggi Alison Felipe Bordini, Dos Santos Matheus Henrique, da Silva-Januário Mara Elisama, Picanço E Castro Virginia

机构信息

Center for Cell-Based Therapy - CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, São Paulo, Brazil.

出版信息

Methods Mol Biol. 2025;2930:267-275. doi: 10.1007/978-1-0716-4558-1_19.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a groundbreaking immunotherapeutic approach to cancer treatment. However, despite its remarkable results, challenges persist, such as manufacturing complexity, side effects, and cost. Allogeneic therapies offer potential solutions to these challenges by enhancing accessibility, reducing cost, and increasing scalability. Due to their innate cytotoxicity and reduced risks of side effects to the patients, natural killer cells are an up-and-coming option for allogeneic CAR therapy. The NK-92 cell line use allows large-scale expansion suitable for clinical grade applications, providing a uniform and highly cytotoxic source. Nevertheless, gene delivery using viral vectors is still an obstacle related to CAR-NK therapies due to their natural antiviral activity. Thus, the present protocol offers an efficient approach for CAR-NK-92 cell generation via lentiviral transduction, thereby advancing the potential of this promising cancer therapy.

摘要

嵌合抗原受体(CAR)-T细胞疗法已成为一种开创性的癌症免疫治疗方法。然而,尽管取得了显著成果,但挑战依然存在,如制造复杂性、副作用和成本等问题。异基因疗法通过提高可及性、降低成本和增加可扩展性,为这些挑战提供了潜在的解决方案。由于其固有的细胞毒性以及对患者副作用风险较低,自然杀伤细胞是异基因CAR疗法中一个崭露头角的选择。使用NK-92细胞系可实现大规模扩增,适用于临床级应用,提供了一个均匀且具有高度细胞毒性的来源。尽管如此,由于NK细胞具有天然抗病毒活性,使用病毒载体进行基因递送仍是与CAR-NK疗法相关的一个障碍。因此,本方案提供了一种通过慢病毒转导生成CAR-NK-92细胞的有效方法,从而推动了这种有前景的癌症治疗方法的潜力。

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