Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padua, Padua, Italy.
Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padua, Padua, Italy; Department of Clinical and Experimental Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Cytokine Growth Factor Rev. 2017 Aug;36:99-105. doi: 10.1016/j.cytogfr.2017.06.003. Epub 2017 Jun 3.
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells. Additionally, their antitumor activity can be redirected and further improved with chimeric antigen receptors, clinical-grade monoclonal antibodies or immune checkpoint inhibitors. The evidence obtained from a growing body of literature support CIK cells as a very promising cell population for adoptive immunotherapy. In this review, all these aspects will be addressed with a particular emphasis on the role of the cytokines involved in CIK cell generation, expansion and functionalization.
细胞因子诱导的杀伤（CIK）细胞在细胞抗肿瘤治疗中引起了越来越多的兴趣，因为它们可以通过简单且廉价的方案轻松扩增，并且非常安全，仅需使用符合 GMP 标准的细胞因子即可获得大量的细胞毒性细胞。CIK 细胞不需要抗原特异性刺激来激活和增殖，因为它们通过 NKG2D 的参与以 HLA 非依赖的方式识别和破坏肿瘤细胞。在几项临床前研究和临床试验中，与常规 T 细胞相比，CIK 细胞显示出较低的同种异体反应性，即使在 HLA 障碍的情况下也是如此；仅在少数患者中，在用同种异体 CIK 细胞治疗后会发生轻度移植物抗宿主病。此外，它们的抗肿瘤活性可以通过嵌合抗原受体、临床级单克隆抗体或免疫检查点抑制剂进行重定向和进一步改善。越来越多的文献证据支持 CIK 细胞作为过继免疫治疗非常有前途的细胞群体。在这篇综述中，将特别强调涉及 CIK 细胞生成、扩增和功能化的细胞因子的作用，讨论所有这些方面。
