一项关于用自体γδ T 细胞进行过继免疫治疗复发性非小细胞肺癌患者的 I 期研究。

A phase I study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous gammadelta T cells.

机构信息

Department of Cardiothoracic Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

出版信息

Eur J Cardiothorac Surg. 2010 May;37(5):1191-7. doi: 10.1016/j.ejcts.2009.11.051.

DOI:10.1016/j.ejcts.2009.11.051

PMID:20137969

Abstract

OBJECTIVES

Human gammadelta T lymphocytes can recognise and kill non-small-cell lung cancer cells by Vgamma9Vdelta2 T-cell receptor and/or NKG2D. We have established large-scale ex vivo expansion of gammadelta T cells by zoledronate and interleukin-2. This pilot feasibility study evaluates the safety and potential anti-tumour effects of activated autologous gammadelta T cells administered intravenously to patients.

METHODS

Patients who had measurable foci of recurrent non-small-cell lung cancer were registered to undergo gammadelta T-cell immunotherapy, designed as a one-way, open, clinical research, after their informed consent. Mononuclear cells collected from peripheral blood of the patient were cultured with zoledronic acid and interleukin-2. After 2-week incubation, the gammadelta T-cell fraction was proliferated and it was intravenously reinfused to the patient.

RESULTS

Ten patients had undergone the gammadelta T-cell immunotherapy. They were administered autologous gammadelta T cells 3-12 times (mean=6) every 2 weeks. No patient died during the study period. Adverse events, not directly related to the immunotherapy, were observed five times in four patients (grade 3 pneumonia in two and grade 1 coldness in three). According to the Response Evaluation Criteria in Solid Tumours, neither complete nor partial response was achieved in any patient; stable disease was observed in three; and progressive disease in five at 4 weeks after six consecutive injections of during immunotherapy. The Functional Assessment of Cancer Therapy-Biologic Response Modifier scores of the patients during immunotherapy were stable or improved, except for one patient who had suffered from pneumonia. The patients were followed up after immunotherapy for 240-850 days (median=401 days). At the end of the observation, six patients were alive.

CONCLUSIONS

We suggest that gammadelta T-cell immunotherapy might be safe and feasible for patients with recurrent non-small-cell lung cancer.

摘要

目的

人类 γδ T 淋巴细胞可通过 Vγ9Vδ2 T 细胞受体和/或 NKG2D 识别并杀伤非小细胞肺癌细胞。我们已经建立了唑来膦酸和白细胞介素-2 大规模体外扩增 γδ T 细胞的方法。这项初步可行性研究评估了静脉内给予活化的自体 γδ T 细胞对复发性非小细胞肺癌患者的安全性和潜在抗肿瘤作用。

方法

在获得患者知情同意后，登记了可测量复发性非小细胞肺癌病灶的患者进行 γδ T 细胞免疫治疗，设计为单向、开放、临床研究。从患者外周血中采集单核细胞，用唑来膦酸和白细胞介素-2 培养。孵育 2 周后，γδ T 细胞部分增殖，并静脉回输给患者。

结果

10 例患者接受了 γδ T 细胞免疫治疗。他们每 2 周接受 3-12 次（平均 6 次）自体 γδ T 细胞治疗。研究期间无患者死亡。在 4 例患者中观察到 5 次与免疫治疗无关的不良事件（2 例 3 级肺炎和 3 例 1 级感冒）。根据实体瘤反应评估标准，任何患者均未达到完全或部分缓解；3 例患者疾病稳定；5 例患者在免疫治疗期间连续 6 次注射后 4 周疾病进展。在免疫治疗期间，患者的癌症治疗功能评估-生物反应调节剂评分稳定或改善，除 1 例发生肺炎的患者外。免疫治疗后对患者进行了 240-850 天（中位 401 天）的随访。在观察结束时，6 例患者存活。