Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, Via G. Gaslini, 516147 Genova, Italy.
Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Cells. 2020 Jul 22;9(8):1757. doi: 10.3390/cells9081757.
Most studies on genetic engineering technologies for cancer immunotherapy based on allogeneic donors have focused on adaptive immunity. However, the main limitation of such approaches is that they can lead to severe graft-versus-host disease (GvHD). An alternative approach would bolster innate immunity by relying on the natural tropism of some subsets of the innate immune system, such as γδ T and natural killer (NK) cells, for the tumor microenvironment and their ability to kill in a major histocompatibility complex (MHC)-independent manner. γδ T and NK cells have the unique ability to bridge innate and adaptive immunity while responding to a broad range of tumors. Considering these properties, γδ T and NK cells represent ideal sources for developing allogeneic cell therapies. Recently, significant efforts have been made to exploit the intrinsic anti-tumor capacity of these cells for treating hematologic and solid malignancies using genetic engineering approaches such as chimeric antigen receptor (CAR) and T cell receptor (TCR). Here, we review over 30 studies on these two approaches that use γδ T and NK cells in adoptive cell therapy (ACT) for treating cancer. Based on those studies, we propose several promising strategies to optimize the clinical translation of these approaches.
大多数基于异体供体的癌症免疫治疗基因工程技术的研究都集中在适应性免疫上。然而，这些方法的主要限制是它们可能导致严重的移植物抗宿主病（GvHD）。另一种方法是通过依赖先天免疫系统的某些亚群的天然趋向性来增强先天免疫，例如 γδ T 和自然杀伤（NK）细胞，以适应肿瘤微环境及其以主要组织相容性复合体（MHC）独立的方式杀死的能力。γδ T 和 NK 细胞具有独特的能力，可以在对广泛的肿瘤作出反应的同时，桥接先天免疫和适应性免疫。考虑到这些特性，γδ T 和 NK 细胞是开发同种异体细胞疗法的理想来源。最近，人们做出了巨大的努力，利用这些细胞的内在抗肿瘤能力，通过基因工程方法（如嵌合抗原受体（CAR）和 T 细胞受体（TCR）），开发用于治疗血液系统恶性肿瘤和实体恶性肿瘤的同种异体细胞疗法（ACT）。在这里，我们回顾了 30 多项关于使用 γδ T 和 NK 细胞进行过继细胞治疗（ACT）治疗癌症的这两种方法的研究。基于这些研究，我们提出了几种有前途的策略来优化这些方法的临床转化。
