新型自体T细胞回输治疗晚期实体肿瘤的安全性及疗效分析  

The safety and efficacy of a novel autologous T cell therapy for advanced malignant solid tumors

作　　者：李伟 卢莉莉 肖淑秀 白金金 王志明 程莉莎 宋正清 吴伟忠[2] 周宇红 LI Wei;LU Li-li;XIAO Shu-xiu;BAI Jin-jin;WANG Zhi-ming;CHENG Li-sha;SONG Zheng-qing;WU Wei-zhong;ZHOU Yu-hong(Department of Medical Oncology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Biotherapeutic Center,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Medical Oncology,Xiamen Branch,Zhongshan Hospital,Fudan University,Xiamen 361015,Fujian,China)

机构地区：[1]复旦大学附属中山医院肿瘤内科,上海200032 [2]复旦大学附属中山医院生物治疗中心,上海200032 [3]复旦大学附属中山医院厦门医院肿瘤内科,厦门361015

出　　处：《中国临床医学》2021年第5期808-812,共5页Chinese Journal of Clinical Medicine

基　　金：上海市自然科学基金(18ZR1406200).

摘　　要：目的:探讨采用程序性死亡因子-1(programmed cell death-1,PD-1)单克隆抗体、白细胞介素2(IL-2)及IL-15诱导制备的新型自体T细胞免疫治疗晚期实体肿瘤的疗效及安全性。方法:前瞻性入组2018年3月至2020年12月复旦大学附属中山医院收治的进行单独新型自体T细胞治疗及新型自体T细胞治疗联合标准治疗的晚期实体肿瘤患者10例,进行Ⅰ期临床研究。主要观察指标为安全性,即治疗相关不良反应的发生率和严重程度;次要观察指标为有效性,包括生活质量评分、无进展生存期等,并分析治疗后患者免疫状态变化。结果:10例患者中包括肝细胞肝癌3例、肠道肿瘤5例、胰腺癌1例和肺癌1例。细胞治疗后28 d内,未发生与治疗有关的严重不良事件。生活质量调查问卷显示,细胞治疗后,患者生活质量改善。其中,躯体功能、总体健康状况、疲倦改善较明显(P<0.05)。3例单用新型T细胞治疗的患者均短期内出现疾病进展;联合治疗患者的疾病控制率为71.4%。联合治疗无效患者的外周血调节性T细胞(Treg)处于较高水平,治疗后28 d高于治疗有效患者(P=0.03)。结论:新型自体T细胞治疗实体肿瘤安全可靠,具有一定的抗肿瘤作用,联合标准治疗可显示良好的疗效,值得进一步扩大研究。Objective:To explore the efficacy and safety of a novel adoptive T cell therapy induced by PD-1 mAb,IL-2,and IL-15 in treatment with the solid tumors.Methods:A single center,prospective,exploratory phaseⅠstudy was conducted.Patients with advanced solid tumors had undergone a novel T-cell therapy alone or the novel T-cell therapy combined with treatment from March 2018 to December 2020 in Zhongshan Hospital,Fudan University.The primary index was safety,such as the incidence and severity of adverse effects.Secondary index was effectiveness,including quality of life scores and progression free survival.And the change of immune status of patients during treatment was analyzed.Results:Ten patients were enrolled,including 3 patients with hepatocellular carcinoma,5 with intestinal tumor,1 with pancreatic cancer,and 1with lung cancer.No treatment-related severe adverse events occurred within 28 days after cell infusion.The qualities of life of all patients were improved after cell therapy,especially in improvement of somatic function,general health,tiredness(P<0.05).Disease progressed in all 3 patients treated with novel T-cell therapy alone.The disease control rate in patients treated with combined therapy was 71.4%.In the nonresponse patients underdoing combined treatment,the percent of Treg in peripheral blood was higher than that in response patients(baseline:P=0.06,28-days after treatment:P=0.03).Conclusions:Novel autologous T cells generated by PD-1 mAb,IL-2,and IL-15 induction,are safe and manageable and show some anti-tumor effects.The combination of novel autologous T cells and standard therapy has shown good efficacy.

关 键 词：实体肿瘤 过继性细胞免疫治疗 程序性死亡因子-1 T细胞 

分 类 号：R730.5[医药卫生—肿瘤]