管社会不断发展,医疗技术不断更新,但癌症仍是导致死亡的首要原因。手术、放疗和化疗是治疗癌症的几种常规疗法,然而,这些方式仍然存在一定的风险性和副作用。免疫疗法已在2013年被列为科学界的重大突破,它是对抗癌症的一种新疗法,其旨在稳定患者的免疫系统,从而更好的抵抗癌症。随着基础与转化医学的快速发展与研究,上千万的癌症患者终将受益其中。

T细胞在抗?肿瘤免疫应答中发挥重要作用。首先,抗原呈递细胞加工并吸收了肿瘤特异性抗原。当这些抗原都显示在APCs表面下主要组织相容性复合体I类和II类分子中时,肿瘤细胞就会被CD4 CD8 T细胞所识别。随后,T细胞就会迅速增多并通过识别免疫刺激信号杀死肿瘤细胞。为了避免长期性暴露抗原,免疫反应结束后,共抑制信号逐渐恢复并阻止T细胞活化。识别肿瘤特异性细胞以及平衡共刺激/抑制受体对于T细胞功能至关重要。

肿瘤细胞建立了一系列的免疫逃逸机制以防止被免疫系统所消灭。免疫疗法的基本原则之一就是利用免疫系统识别并杀死肿瘤细胞。免疫疗法基于T细胞嵌合抗原受体和两大免疫检查点,即细胞毒性T淋巴细胞相关抗原4CTLA4)和程序死亡1PD1,从而取得了显著的临床研究成果。与基于CTLA4的免疫疗法相比,基于PD1的免疫疗法副作用更小,抗肿瘤活性更强。因此,本研究重点讨论基于CAR Chimeric Antigen ReceptorT 细胞和基于PD1(Programmed Death 1) 的两种免疫疗法。

 

Review of Cancer Immunotherapy: Application of Chimeric Antigen Receptor T Cells and Programmed Death 1/Programmed Death-ligand 1 Antibodies

 

Tengfei Zhang1,2, Ling Cao1, Zhen Zhang1, Dongli Yue1, Yu Ping1, Hong Li1, Lan Huang1,Yi Zhang1,3,4,5
1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;2Department of Hematology and Oncology, Harvard Medical School, Boston, MA, USA; 3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; 4Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China; 5School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China

Cancer immunotherapy strategies based on chimeric antigen receptor (CAR) transduced T cells or antibodies against immune checkpoints, cytotoxic T?lymphocyte?associated antigen 4 (CTLA?4) and programmed death 1 (PD?1), achieved significant successes from bench to clinic in the past 2 years. CARs are artificial engineered receptors that can specifically target tumor cell surface antigen, activate T cell and further enhance T cell function, independent of major histocompatibility complex. CAR T cells have shown promising outcomes in cancers, especially in hematologic malignancies. CTLA?4 and PD?1 are two important immune checkpoints negatively regulating T cell activation. Clinical benefits of CTLA?4/PD?1 antibodies are significant in melanoma and other solid tumors. PD?1 is predicted to have fewer side effects and greater antitumor activity than CTLA?4. In this review, we will summarize current immunotherapies based on CAR T cells and PD?1.
Keywords: Cancer immunotherapy, chimeric antigen receptor T cells, programmed death 1

From:Cancer Translational Medicine 2015;1(2):43–49