细胞因子诱导的杀伤细胞治疗晚期肺癌的临床观察
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摘要
目的:探讨细胞因子诱导的杀伤细胞(CIK)在晚期肺癌治疗中的临床安全性和疗效。方法:59例晚期肺癌患者按照治疗方法不同分为两组。29例(对照组)接受传统的以铂类为基础的双药联合化疗。30例(CIK组)接受传统治疗和CIK回输治疗。采集患者外周血50～100 m L,按照标准流程体外诱导为CIK细胞,根据临床治疗方案静脉回输。观察两组患者的不良反应,随访并评价临床疗效。结果:CIK组患者均未出现严重的不良反应; 8例患者出现一过性的发热,对症处理后迅速好转,2例患者分别出现寒战和乏力。与对照组相比,CIK细胞输注之后,患者的精神及体力方面改善(P <0. 05)。CIK组2例患者病灶缩小。两组生存曲线差异有统计学意义(P=0. 041),CIK组中位生存期(29个月)明显长于对照组(12个月)。结论:CIK细胞治疗可以提高晚期肺癌患者的生活质量并延长总体生存期,临床不良反应较轻微,大部分患者能够耐受。
Aim: To evaluate the clinical safety and efficiency of cytokine-induced killer cell(CIK) in the treatment of advanced-stage lung cancer. Methods: Fifty-nine patients with advanced-stage lung cancer were recruited and allocated into two groups according to the different treatments. Thirty patients(the CIK group) received conventional therapy in the form of chemotherapy and CIK therapy(50-100 m L peripheral blood were collected from lung cancer patients and cultured into anti-tumor immune cells according to the CIK standard procedure in vitro; administering CIK intravenously under the clinical design). Twenty-nine patients(control group) received conventional therapy alone. The side effects were observed,and clinical response was evaluated. Results: No serious side effects were observed in all the patients receiving CIK infusion.Eight patients presented transient fever after treatment and recovered soon. Two patients presented chill and fatigue,respectively. Compared with control group,the mental status and energy improved after infusing CIK(P < 0. 05),as well as tumor shrinkage was observed in two patients. Moreover,the survival curve of the 2 groups had significant difference(P <0. 05). The median survival of the CIK group(29 months) was longer than control group(12 months). Conclusion: CIK therapy could improve life quality and prolong overall survival time with mild and tolerable side effects.
Aim: To evaluate the clinical safety and efficiency of cytokine-induced killer cell(CIK) in the treatment of advanced-stage lung cancer. Methods: Fifty-nine patients with advanced-stage lung cancer were recruited and allocated into two groups according to the different treatments. Thirty patients(the CIK group) received conventional therapy in the form of chemotherapy and CIK therapy(50-100 m L peripheral blood were collected from lung cancer patients and cultured into anti-tumor immune cells according to the CIK standard procedure in vitro; administering CIK intravenously under the clinical design). Twenty-nine patients(control group) received conventional therapy alone. The side effects were observed,and clinical response was evaluated. Results: No serious side effects were observed in all the patients receiving CIK infusion.Eight patients presented transient fever after treatment and recovered soon. Two patients presented chill and fatigue,respectively. Compared with control group,the mental status and energy improved after infusing CIK(P < 0. 05),as well as tumor shrinkage was observed in two patients. Moreover,the survival curve of the 2 groups had significant difference(P <0. 05). The median survival of the CIK group(29 months) was longer than control group(12 months). Conclusion: CIK therapy could improve life quality and prolong overall survival time with mild and tolerable side effects.
引文
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[14]KHAMMARI A,KNOL AC,NGUYEN JM,et al.Adoptive TIL transfer in the adjuvant setting for melanoma:longterm patient survival[J].J Immunol Res,2014,2014:186212
[15]WOLCHOK JD,HOOS A,O'DAY S,et al.Guidelines for the evaluation of immune therapy activity in solid tumors:immune-related response criteria[J].Clin Cancer Res,2009,15(23):7412
[16]SANMAMED MF,PEREZ-GRACIA JL,SCHALPER KA,et al.Changes in serum interleukin-8(IL-8)levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients[J].Ann Oncol,2017,28(8):1988
[17]HODI FS,HWU WJ,KEFFORD R,et al.Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab[J].J Clin Oncol,2016,34(13):1510
[2]CHEN WQ,ZENG HM,ZHENG RS,et al.Cancer incidence and mortality in China,2007[J].Chin J Cancer Res,2012,24(1):1
[3]CHEN W,ZHENG R,BAADE PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115
[4]郭振红,曹雪涛.肿瘤免疫细胞治疗的现状及展望[J].中国肿瘤生物治疗杂志,2016,23(2):149
[5]LI H,HUANG L,LIU LB,et al.Selective effect of cytokine-induced killer cells on survival of patients with earlystage melanoma[J].Cancer Immunol Immunother,2017,66(3):299
[6]HUANG JM,KAN QC,HUANG L,et al.Chemotherapy in combination with cytokine-induced killer cell transfusion:an effective therapeutic option for patients with extensive stage small cell lung cancer[J].Int Immunopharmacol,2017,46:170
[7]NGUYEN LT,SAIBILSD,SOTOV V,et al.PhaseⅡclinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2[J].Cancer Immunol Immunother,2019,68(5):773
[8]张毅,刘艳粉.嵌合抗原受体T细胞治疗实体瘤的现状和挑战[J].郑州大学学报(医学版),2018,53(6):701
[9]INTRONA M.CIK as therapeutic agents against tumors[J].J Autoimmun,2017,85:32
[10]ZHAO X,ZHANG Z,LI H,et al.Cytokine induced killer cellbased immunotherapies in patients with different stages of renal cell carcinoma[J].Cancer Lett,2015,362(2):192
[11]OBLEUKHOVA I,KIRYISHINA N,FALALEEVA SA,et al.Use of antigen-primed dendritic cells for inducing antitumor immune responses in vitro in patients with non-small cell lung cancer[J].Oncol Lett,2018,15(1,B):1297
[12]GUO LM,XU DH,LU Y,et al.Detection of circulating tumor cells by reverse transcription-quantitative polymerase chain reaction and magnetic activated cell sorting in the peripheral blood of patients with hepatocellular carcinoma[J].Mol Med Rep,2017,16(5):5894
[13]LIU J,LI H,CAO S,et al.Maintenance therapy with autologous cytokine-induced killer cells in patients with advanced epithelial ovarian cancer after first-line treatment[J].J Immunother,2014,37(2):115
[14]KHAMMARI A,KNOL AC,NGUYEN JM,et al.Adoptive TIL transfer in the adjuvant setting for melanoma:longterm patient survival[J].J Immunol Res,2014,2014:186212
[15]WOLCHOK JD,HOOS A,O'DAY S,et al.Guidelines for the evaluation of immune therapy activity in solid tumors:immune-related response criteria[J].Clin Cancer Res,2009,15(23):7412
[16]SANMAMED MF,PEREZ-GRACIA JL,SCHALPER KA,et al.Changes in serum interleukin-8(IL-8)levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients[J].Ann Oncol,2017,28(8):1988
[17]HODI FS,HWU WJ,KEFFORD R,et al.Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab[J].J Clin Oncol,2016,34(13):1510