Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors.
Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors.
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DOI：
10.3390/cancers13112796
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发表时间：
2021-06-04
期刊：
影响因子：
5.2
通讯作者：
Capitini CM
中科院分区：
文献类型：
--
作者：
Quamine AE;Olsen MR;Cho MM;Capitini CM
患有转移性实体瘤的儿童通常预后很差，特别是当癌症复发或对前期治疗有抵抗力时。希望免疫系统中的细胞可以被编程来帮助患者识别和消除他们的癌症。自然杀伤（NK）细胞是免疫系统的重要组成部分，旨在消除病毒感染的细胞和肿瘤。在过去的20年里，细胞制造的进步使研究人员能够在实验室中大量培养NK细胞，并将这些细胞改造成高效细胞。虽然一些在患有实体瘤的儿童中使用NK细胞的临床试验显示出了希望，但我们仍然需要学习如何有效地使用NK细胞。这篇综述将讨论我们目前对NK细胞生物学的理解及其与通常影响儿童的实体瘤的相关性。转移性儿科实体瘤的治疗仍然是一个重大挑战，特别是在复发性和难治性环境中。标准治疗包括手术切除、放疗、化疗，以及神经母细胞瘤的免疫治疗。尽管有这样的强化治疗，癌症复发是常见的，并且大多数肿瘤对先前的治疗变得难治，使患者几乎没有常规治疗选择。自然杀伤（NK）细胞是非主要组织相容性复合体（MHC）限制性淋巴细胞，其具有几种复杂的杀伤机制，但具有不引起移植物抗宿主病的额外优势，使同种异体NK细胞成为潜在的治疗选择。除了它们的杀伤能力之外，NK细胞还产生几种细胞因子和生长因子，这些细胞因子和生长因子充当适应性免疫系统的关键调节因子，将它们自身定位为刺激大量预处理的免疫系统的理想效应细胞。尽管如此，迄今为止过继性NK细胞疗法的临床疗效一直不一致，促使人们详细了解NK细胞内的生物学途径，这些途径可用于开发“下一代”NK细胞疗法。在这里，我们回顾了目前优化NK细胞抗肿瘤反应的方法的进展，包括与其他免疫疗法，细胞因子，检查点抑制和工程NK细胞与嵌合抗原受体（汽车）治疗儿科实体瘤。
Children with metastatic solid tumors typically have a very poor prognosis, especially when the cancer returns or is resistant to upfront treatment. There is hope that the cells in the immune system can be programmed to help patients recognize and eliminate their cancer. Natural killer (NK) cells are an important component of the immune system designed to eliminate virally infected cells and tumors. In the last 20 years, advances in cell manufacturing have allowed investigators to grow NK cells in the laboratory to high numbers and engineer the cells to become highly potent. While some clinical trials using NK cells in children with solid tumors have shown promise, we still have much to learn on how to use NK cells effectively. This review will discuss our current understanding of NK cell biology and its relevance to solid tumors that commonly affect children. Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options. Natural killer (NK) cells are non-major histocompatibility complex (MHC)-restricted lymphocytes that boast several complex killing mechanisms but at an added advantage of not causing graft-versus-host disease, making use of allogeneic NK cells a potential therapeutic option. On top of their killing capacity, NK cells also produce several cytokines and growth factors that act as key regulators of the adaptive immune system, positioning themselves as ideal effector cells for stimulating heavily pretreated immune systems. Despite this promise, clinical efficacy of adoptive NK cell therapy to date has been inconsistent, prompting a detailed understanding of the biological pathways within NK cells that can be leveraged to develop “next generation” NK cell therapies. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors.
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DOI：
10.1158/1078-0432.ccr-10-0735
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cho D;Shook DR;Shimasaki N;Chang YH;Fujisaki H;Campana D
通讯作者：
Campana D
影响因子：
7.3
作者：
Bálint Š;Lopes FB;Davis DM
通讯作者：
Davis DM
影响因子：
5.8
作者：
Boerman, Gerharda H.;van Ostaijen-ten Dam, Monique M.;van Tol, Maarten J. D.
通讯作者：
van Tol, Maarten J. D.
影响因子：
8
作者：
Cichocki, Frank;Tams, Emily;Miller, Jeffrey S.
通讯作者：
Miller, Jeffrey S.
影响因子：
7.3
作者：
Bartel Y;Bauer B;Steinle A
通讯作者：
Steinle A