工程化自然杀伤细胞治疗癌症及其在癌症治疗之外的潜在应用

Engineered NK Cells Against Cancer and Their Potential Applications Beyond.

机构信息

Center for Hematology and Regenerative Medicine, Department of Medicine-Huddinge, Karolinska Institute, Stockholm, Sweden.

Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.

出版信息

Front Immunol. 2022 Feb 15;13:825979. doi: 10.3389/fimmu.2022.825979. eCollection 2022.

Abstract

Cell therapy is an innovative therapeutic concept where viable cells are implanted, infused, or grafted into a patient to treat impaired or malignant tissues. The term was first introduced circa the 19 century and has since resulted in multiple breakthroughs in different fields of medicine, such as neurology, cardiology, and oncology. Lately, cell and gene therapy are merging to provide cell products with additional or enhanced properties. In this context, adoptive transfer of genetically modified cytotoxic lymphocytes has emerged as a novel treatment option for cancer patients. To this day, five cell therapy products have been FDA approved, four of which for CD19-positive malignancies and one for B-cell maturation antigen (BCMA)-positive malignancies. These are personalized immunotherapies where patient T cells are engineered to express chimeric antigen receptors (CARs) with the aim to redirect the cells against tumor-specific antigens. CAR-T cell therapies show impressive objective response rates in clinical trials that, in certain instances, may reach up to 80%. However, the life-threatening side effects associated with T cell toxicity and the manufacturing difficulties of developing personalized therapies hamper their widespread use. Recent literature suggests that Natural Killer (NK) cells, may provide a safer alternative and an 'off-the-shelf' treatment option thanks to their potent antitumor properties and relatively short lifespan. Here, we will discuss the potential of NK cells in CAR-based therapies focusing on the applications of CAR-NK cells in cancer therapy and beyond.

摘要

细胞治疗是一种创新的治疗概念,通过将有活力的细胞植入、输注或移植到患者体内,来治疗受损或恶性组织。该术语最早于 19 世纪引入,此后在神经学、心脏病学和肿瘤学等多个医学领域取得了多项突破。最近,细胞和基因治疗正在融合,以提供具有额外或增强特性的细胞产品。在这种情况下,经过基因修饰的细胞毒性淋巴细胞的过继转移已成为癌症患者的一种新的治疗选择。迄今为止,已有五种细胞治疗产品获得美国食品药品监督管理局(FDA)批准,其中四种用于 CD19 阳性恶性肿瘤,一种用于 B 细胞成熟抗原(BCMA)阳性恶性肿瘤。这些是个性化免疫疗法,通过对患者的 T 细胞进行工程改造,使其表达嵌合抗原受体(CAR),从而使细胞能够针对肿瘤特异性抗原进行重定向。CAR-T 细胞疗法在临床试验中显示出令人印象深刻的客观缓解率,在某些情况下,其缓解率可能高达 80%。然而,与 T 细胞毒性相关的危及生命的副作用以及开发个性化疗法的制造困难限制了它们的广泛应用。最近的文献表明,自然杀伤(NK)细胞由于其强大的抗肿瘤特性和相对较短的寿命,可能提供一种更安全的替代方案和“现成的”治疗选择。在这里,我们将讨论 NK 细胞在基于 CAR 的疗法中的潜力,重点讨论 CAR-NK 细胞在癌症治疗及其他领域的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f1f/8887605/eb886392d012/fimmu-13-825979-g001.jpg

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