Clinical research on a new immunotherapy for the treatment of non-small cell lung cancer

本研究旨在探讨活化自体γ-增量T淋巴细胞(GDT)免疫治疗复发性非小细胞肺癌的安全性和抗肿瘤效果。观察到GDT的数量大约增加了1000倍，占培养的单个核细胞总数的85%到95%。该GDT组分表达NKG2D，对MICA/B阳性的非小细胞癌(NSCLC)细胞具有细胞毒作用。在本院IRB入院后，我们启动了活化自体GDT治疗难治性NSCLC的临床试验。我们登记了8例在书面知情同意后复发的非小细胞肺癌患者。除2例患者体外培养获得足够数量的GDT外，其余患者均进入临床研究，除1例受试者在试验期间曾患感冒外，其余均未见不良反应。我们发现，在接受FACT-QOL问卷调查的3名患者中，有1名患者在研究过程中生活质量恶化，这主要是由于普通感冒造成的。所有患者都有可测量的复发灶，研究期间计算机断层扫描显示复发灶的大小没有缩小。我们对接受GDT治疗的患者的外周血进行了流式细胞仪检测，我们观察到GDT在治疗过程中数量增加。我们还观察了GDT对表面表达MICA的U266细胞的细胞毒作用。我们证实了NKG2D-MICA/B对患者GDT的细胞毒作用。在本研究中，到目前为止，我们实际上只给每个患者4次激活的GDT。我们认为，增加GDT的剂量将在非小细胞肺癌的免疫治疗方面取得突破。

This study aimed to investigate the safety and antitumor effect of the new immunotherapy with activated autologous gamma delta T-lymphocyte (GDT) on the patients suffering from recurrent non-small cell lung cancer. Approximately 1000-folds increase of the number GDT, comprising 85 to 95% of whole cultured mononuclear cells, was observed. This GDT fraction expresses NKG2D, showing cytotoxic effect against MICA/B-positive non-small cell cancer (NSCLC) cell lines.Under the admission of IRB in this hospital, we started the clinical trial on the treatment of refractory NSCLC with activated autologous GDT. We registered 8 patients with recurrent NSCLC after the documented informed consent. All except for 2 patients who attained enough number of GDT after in vitro culture were assigned to this clinical investigation.We observed no harmful complications after administration of cultured GDT, except for one case who had suffered from common cold during the trial period, which were not related to the GDT therapy. We found that one of 3 patients who had undergone FACT-QOL questionnaire had exacerbation of QOL during the study, which were mainly due to the common cold.All of the patients had measurable foci of recurrence, which were not decreased in size by Computed tomography during the study. We performed flow-cytometry study of the peripheral blood of the patients undergoing GDT therapy, and we observed that number of GDT was increased during the therapy. We also observed cytotoxic effect of the GDT against U266 cell line which expresses MICA on the surface. We confirmed that NKG2D-MICA/B cytotoxic effect on GDT of the patients.In this study so far, we actually gave each patient the activated GDT only 4 times. We suggest that increment of the dosage of GDT would make breakthrough on the immunotherapy of NSCLC.