DC疫苗联合细胞因子诱导的杀伤细胞治疗转移性肾癌的长期疗效分析

Long-term efficacy of dendritic cell vaccines combined with cytokine-induced killer cells in the treatment of metastatic renal cell carcinoma

目的:评价树突状细胞(DC)疫苗联合细胞因子诱导的杀伤(CIK)细胞治疗转移性肾癌的长期临床疗效及随访观察。方法:选择2011 年1 月至2013 年12 月于中国人民解放军总医院第五医学中心造血干细胞移植科接受DC疫苗联合CIK细胞治疗的29 例转移性肾癌患者,其中男性24 例、女性5 例,中位年龄55 岁(32~81 岁)。一线治疗12 例,分子靶向药物或细胞因子治疗进展后二线治疗6 例,三线及以上治疗11 例(包括二次手术治疗、细胞因子治疗和多线分子靶向药物治疗)。通过基因转染技术获得成熟的DC疫苗,体外细胞培养技术获得CIK细胞,经淋巴引流区及静脉输注方式按疗程回输患者体内,评价其长期临床疗效及总体生存率。结果:29 例患者中位随访时间5 年(1~7 年)。治疗疗程≥2(2~23 个疗程)。疗效评价:完全缓解1 例(3.4%),部分缓解9 例(31%),疾病稳定13 例(44.8%),疾病进展6 例(20.7%)。客观反应率34.4%,疾病控制率79.2%。疾病稳定1年以上19 例(65.5%)。1、3、5 年生存率分别为93.1%(27/29)、65.5%(20/29)和51.7%(15/29)。中位无进展生存期及中位生存期均未达到。治疗期间均未观察到3 级以上不良反应发生。结论:DC疫苗联合CIK细胞治疗转移性肾细胞癌疗效肯定,可获得良好的疾病控制率及长期生存,安全性可控,延长了晚期肾癌患者的生存期。

Objective: To evaluate the long-term clinical efficacy and follow-up of dendritic cell (DC) vaccines in combination with cytokine-induced killer cell (CIK) treatment in metastatic renal cell carcinoma. Methods: From January 2011 to December 2013, 29 patients with metastatic renal cell carcinoma (pathologically confirmed as renal clear cell carcinoma) were treated by DC vaccines-CIK at the Department of Hematopoietic Stem Cell Transplantation, the Fifth Medical Center of Chinese PLA General Hospital. The 29 patients included 24 male and 5 female, with a median age of 57(32-81) years old. Mature DC vaccine was obtained by gene transfection technology and CIK cells were obtained by in vitro culture;and DC vaccine-CIK was infused back to patients through lymphatic drainage area and vein by each course. Twelve patients received first line treatment, 6 patients received second line treatment after the disease progression by targeted drug therapy or cytokine therapy, and 11 patients received third-linetreatment or above. The long-term clinical efficacy and overall survival rate were evaluated. Results: The median follow-up time was 5 (1-7) years. Treatment cycle was over 2 (2-23) cycles. One case (3.4%) achieved complete remission, 9 cases (31%) achieved partial responses, 13 cases (44.8%) demonstrated stable disease over 3 months and 6 patients (20.7%) developed progressive disease. The objective response rate was 34.4%,and the disease control rate was 79.2%. Stable disease for more than one year realized in 19 cases (65.5%). The 1-, 3- and 5-year survival rates were 93.1%(27/29), 65.5%(20/29) and 51.7%(15 / 29), respectively. Neither the median progression-free survival (PFS) nor the median survival time was achieved. No adverse reactions above grade 3 were observed during treatment. Conclusion: DC vaccines-CIK therapy for the treatment of metastatic renal cell carcinoma is affirmative;it achieved good disease control and long-term survival with controllable safety, and prolonged the survival time for advanced renal cell carcinoma patients.