McDowell Kimberly A, Hank Jacquelyn A, DeSantes Kenneth B, Capitini Christian M, Otto Mario, Sondel Paul M
Department of Pediatrics, Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, The University of Wisconsin, Madison, WI.
J Pediatr Hematol Oncol. 2015 Mar;37(2):79-93. doi: 10.1097/MPH.0000000000000303.
The past decade has seen several anticancer immunotherapeutic strategies transition from "promising preclinical models" to treatments with proven clinical activity or benefit. In 2013, the journal Science selected the field of Cancer Immunotherapy as the overall number-1 breakthrough for the year in all of scientific research. In the setting of cancer immunotherapy for adult malignancies, many of these immunotherapy strategies have relied on the cancer patient's endogenous antitumor T-cell response. Although much promising research in pediatric oncology is similarly focused on T-cell reactivity, several pediatric malignancies themselves, or the chemo-radiotherapy used to achieve initial responses, can be associated with profound immune suppression, particularly of the T-cell system. A separate component of the immune system, also able to mediate antitumor effects and less suppressed by conventional cancer treatment, is the NK-cell system. In recent years, several distinct immunotherapeutic approaches that rely on the activity of NK cells have moved from preclinical development into clinical testing, and some have shown clear antitumor benefit. This review provides an overview of NK cell-based immunotherapy efforts that are directed toward childhood malignancies, with an emphasis on protocols that are already in clinical testing.
在过去十年中，已有多种抗癌免疫治疗策略从“有前景的临床前模型”转变为经证实具有临床活性或益处的治疗方法。2013年，《科学》杂志将癌症免疫治疗领域选为当年所有科研领域中的头号重大突破。在针对成人恶性肿瘤的癌症免疫治疗中，许多此类免疫治疗策略都依赖于癌症患者内源性抗肿瘤T细胞反应。尽管儿科肿瘤学中许多有前景的研究同样聚焦于T细胞反应性，但一些儿科恶性肿瘤本身，或用于实现初始反应的放化疗，可能会导致严重的免疫抑制，尤其是T细胞系统。免疫系统的另一个组成部分——NK细胞系统，同样能够介导抗肿瘤作用，且较少受到传统癌症治疗的抑制。近年来，几种依赖NK细胞活性的独特免疫治疗方法已从临床前开发进入临床试验阶段，其中一些已显示出明确的抗肿瘤益处。本综述概述了针对儿童恶性肿瘤的基于NK细胞的免疫治疗研究进展，重点介绍了已进入临床试验阶段的方案。
