Realizing Innate Potential: CAR-NK Cell Therapies for Acute Myeloid Leukemia.
Realizing Innate Potential: CAR-NK Cell Therapies for Acute Myeloid Leukemia.
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实现先天潜能：CAR-NK细胞治疗急性髓性白血病。
DOI：
10.3390/cancers13071568
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发表时间：
2021-03-29
期刊：
影响因子：
5.2
通讯作者：
O'Dwyer M
中科院分区：
文献类型：
--
作者：
Gurney M;O'Dwyer M
对T细胞进行基因改造以识别CD19蛋白(CD19 CAR-T细胞)的输注已被证明是一种有效的癌症治疗形式，可治疗某些由B细胞引发的癌症。这些疗法虽然是革命性的，但使用患者自己的细胞制造仍然昂贵，而且可能会产生相当大的副作用。人们对改进和扩大这些新疗法的覆盖范围到其他癌症类型非常感兴趣。自然杀伤(NK)细胞是一种具有独特性质的替代细胞群，它也可以被修饰以识别特定的蛋白质(CAR-NK细胞)。CAR-NK细胞的特性应该可以快速获得健康的供体细胞，并可能减少副作用。NK细胞具有针对急性髓系白血病(AML)的先天能力。在这篇综述文章中，我们认为CAR-NK细胞具有增强这一效应的潜力，并为AML提供一种新型的免疫治疗。下一代细胞免疫疗法寻求提高经批准的CD19嵌合抗原受体(CAR)T细胞产品的安全性和有效性，或将其原理应用于越来越多的靶点和疾病清单。在充满希望的早期临床经验的支持下，CAR修饰的自然杀伤(CAR-NK)细胞疗法代表了一种补充的、可能是现成的同种异体解决方案。虽然急性髓系白血病(AML)是一种直观的疾病，可以用来研究基于CAR的免疫疗法，但到目前为止，B细胞恶性肿瘤的关键生物学差异已经取得了复杂的进展。随着治疗AML的CAR-T细胞试验数量的增加，几种CAR-NK细胞方法也在开发中。在这篇综述中，我们探索了为什么CAR-NK细胞疗法可能特别适合急性髓系白血病的治疗。首先，我们研究了自然杀伤细胞在急性髓系白血病生物学中的作用，以及自然杀伤细胞过继转移的抗白血病活性。接下来，我们评估潜在的AML靶抗原，并考虑与治疗B细胞恶性肿瘤相关的共同和独特的挑战。我们总结了CAR-NK细胞在AML中发展的现状，以及通过药理学和基因工程加强CAR-NK细胞治疗的潜在靶点。最后，我们考虑AML治疗中相互竞争的免疫治疗方法的更广泛的前景。在这样做的过程中，我们评估了基于CAR-NK的AML免疫治疗的固有潜力、现状和剩余障碍。
Infusions of T-cells genetically modified to recognize the protein CD19 (CD19 CAR-T cells) have proven a potent form of cancer therapy for certain cancers arising from B-cells. These treatments, while revolutionary, remain expensive to manufacture using a patients’ own cells and can have considerable side effects. There is great interest in improving upon and expanding the reach of these new treatments to other cancer types. Natural killer (NK) cells are an alternative cell population with unique properties which can also be modified to recognize specific proteins (CAR-NK cells). The properties of CAR-NK cells should allow manufacturing from healthy donor cells with rapid availability and potentially fewer side effects. NK cells have an innate ability to target acute myeloid leukemia (AML). In this review article, we consider the potential that CAR-NK cells possess to enhance this effect and offer a new type of immunotherapy for AML. Next-generation cellular immunotherapies seek to improve the safety and efficacy of approved CD19 chimeric antigen receptor (CAR) T-cell products or apply their principles across a growing list of targets and diseases. Supported by promising early clinical experiences, CAR modified natural killer (CAR-NK) cell therapies represent a complementary and potentially off-the-shelf, allogeneic solution. While acute myeloid leukemia (AML) represents an intuitive disease in which to investigate CAR based immunotherapies, key biological differences to B-cell malignancies have complicated progress to date. As CAR-T cell trials treating AML are growing in number, several CAR-NK cell approaches are also in development. In this review we explore why CAR-NK cell therapies may be particularly suited to the treatment of AML. First, we examine the established role NK cells play in AML biology and the existing anti-leukemic activity of NK cell adoptive transfer. Next, we appraise potential AML target antigens and consider common and unique challenges posed relative to treating B-cell malignancies. We summarize the current landscape of CAR-NK development in AML, and potential targets to augment CAR-NK cell therapies pharmacologically and through genetic engineering. Finally, we consider the broader landscape of competing immunotherapeutic approaches to AML treatment. In doing so we evaluate the innate potential, status and remaining barriers for CAR-NK based AML immunotherapy.
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影响因子：
11.2
作者：
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