细胞因子诱导的杀伤细胞抗肿瘤研究进展

细胞因子诱导的杀伤细胞（CIK细胞）是将人外周血单个核细胞在体外经多种细胞因子共同诱导而获得的一群异质细胞,又称自然杀伤样T淋巴细胞,具有自然杀伤（NK）细胞的非主要组织相容性复合体（MHC）限制性杀瘤特点和T淋巴细胞强大的抗瘤活性,杀伤活性强,被认为是肿瘤过继免疫治疗的新希望,越来越受到人们的重视。     

基因修饰体细胞国内外临床研究和相关产业现状及未来发展趋势

基因编辑技术可针对性增强体细胞的靶向性,一定程度上解决了传统过继性免疫疗法在肿瘤等多种疾病治疗中显露出的靶向性差等问题.最具代表性的是嵌合抗原受体T细胞(CAR-T)免疫疗法,其在血液系统肿瘤治疗中已取得良好疗效,此外,T细胞受体基因工程化的T细胞(TCR-T)、基因修饰的树突状细胞以及基因修饰的干细胞在多种疾病治疗的...     

CIK细胞体外实验研究及治疗肿瘤的临床疗效

细胞因子诱导的杀伤细胞（cytokine induced killer,CIK）是近年来发现的一种新型抗瘤细胞,以其体外增殖数量大、对肿瘤杀伤活性强、抗瘤谱广、副作用小等特点,逐渐被人们所认识,并应用于临床。本文就CIK细胞体外增殖特性进行了研究并对CIK细胞治疗肿瘤的疗效进行观察。     

DC-CIK细胞免疫治疗的生物学基础及临床应用

细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK)是一非主要组织相容性复合体(MHC)限制性的细胞毒性T淋巴细胞,被认为是肿瘤过继免疫治疗的新希望。而树突状细胞(dendritic cells,DC)是目前所知的人体内功能最强的抗原递呈细(antigen p resenting cell,APC),两者共培养后,显示出强大的协同抗肿瘤作用,已经广泛应用于部分肿瘤中,并取得了一定的临床疗效。     

基于AO/PI荧光染色原理的杀伤细胞数量及活率检测方法学验证和细胞培养、冻存、复苏稳定性研究

目的 验证基于吖啶橙(AO)/碘化丙啶(PI)荧光染色原理的自动细胞分析仪检测细胞因子诱导的杀伤细胞(CIK)数量及活率的可行性,并对 CIK 细胞培养全过程及冻存复苏后至使用前过程进行检测,建立相应的数量及活率标准。方法 采集健康供者的外周血分离、培养 CIK 细胞,取培养过程中的细胞使用 AO/PI 荧光染色法、应用自动细胞分析仪检测细胞数量及活率,对结果的专属性、准确度、精密度、数量线性及范围、活率线性及范围进行验证。应用建立的方法对外周血分离后的外周血单个核细胞(PBMC)、培养过程中、冻存前及复苏后的 CIK 细胞数量及活率进行全过程检测。结果 专属性、准确度、精密度、数量线性及范围、活率线性及范围验证均符合预期要求。CIK 细胞培养全过程活率均不低于 80%,样本平均倍增时间为(42.26±1.17)h。冻存前的 CIK 细胞在加入含 5% DMSO 的冷冻保护剂后 90 min 内活率稳定,复苏后未经稀释或洗涤处理 120 min 内活率稳定,复苏后经洗涤去除 DMSO 处理后 12 h 内活率稳定。结论 基于AO/PI荧光染色原理的自动细胞分析仪可以用于检测 CIK 细胞的数量及活率,其结果可以用于细胞放行评价及稳定性研究。     

DC-CIK细胞免疫治疗配合化疗与单纯化疗治疗卵巢癌的疗效比较

目的比较树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)免疫治疗配合化疗与单纯化疗一线治疗卵巢癌的疗效、不良反应及生存质量。方法 54例经病理或细胞学证实的晚期卵巢癌患者,随机分为治疗组和对照组,每组27例。治疗组采用紫杉醇+卡铂联合化疗,并于化疗间歇期配合DCCIK细胞免疫治疗;对照组仅进行紫杉醇+卡铂单纯化疗。观察并比较两组的疗效、不良反应及患者的生存质量。结果治疗组和对照组的有效率分别为55.6%、51.9%,临床获益率分别为92.6%、85.2%,两组比较差异无统计学意义(P>0.05)。治疗组白细胞下降、口腔黏膜炎的发生率均明显低于对照组,差异有统计学意义(P<0.05)。治疗组的Karnofsky评分和生活质量(QOL)评分较对照组有显著提高,差异有统计学意义(P<0.05)。结论 DC-CIK细胞免疫治疗配合化疗与单纯化疗一线治疗晚期卵巢癌比较,疗效相当,但明显减轻化疗的不良反应,显著提高晚期肿瘤患者的生存质量。     

认知干预对经 DC-CIK 治疗的中晚期肝细胞癌患者生命质量、疼痛程度及临床疗效的影响

目的：研究认知干预对经 DC-CIK 治疗的中晚期肝细胞癌患者的生命质量、疼痛程度及临床疗效的影响。方法选择中国医科大学附属第一医院普通外科及肿瘤内科2011年1月—2014年1月收治的中晚期肝细胞癌156例,随机分为观察组（82例）与对照组（74例）。两组均予肿瘤常规方案、DC-CIK 方案治疗及常规心理干预,观察组同步予认知干预。治疗前后用肿瘤生命质量核心问卷（ QLQ-C30）评估两组生命质量,采用视觉模拟评分法（ VAS）评价两组疼痛程度,评估两组近、远期临床疗效,记录两组中位生存期,观察并记录治疗过程中的不良反应。结果治疗后两组 QLQ-C30整体功能、特异性症状模块各指标及整体生命质量评分均明显优于治疗前（ P ﹤0.05,P ﹤0.01）,治疗后观察组上述指标均优于对照组（P ﹤0.05）;两组治疗后疼痛程度均明显低于治疗前（ P ﹤0.01）,治疗后观察组疼痛程度明显低于对照组（P ﹤0.05）;治疗后两组近期临床疗效差异无统计学意义（ P ﹥0.05）,观察组远期临床疗效优于对照组（P ﹤0.05）,且中位生存期长于对照组（P ﹤0.05）;两组治疗中主要不良反应发生率差异无统计学意义（ P﹥0.05）。结论对于中晚期肝细胞癌患者在进行 DC-CIK 免疫治疗的基础上给予认知干预,能很好改善患者的生命质量、缓解疼痛、提高远期临床疗效,且安全性较高。     

负载MAGE-A3抗原的树突状细胞与细胞因子诱导杀伤细胞共培养对子宫内膜癌肿瘤干细胞及恶性进展的影响

目的:探究负载黑色素瘤相关抗原基因A3(MAGE-A3)的树突状细胞(DC)与细胞因子诱导杀伤细胞(CIK)对子宫内膜癌肿瘤干细胞及恶性进展的影响。方法:采集人外周血分离单个核细胞,利用细胞因子分别诱导生成DC和CIK;MAGE-A3孵育DC后与CIK共培养,流式细胞仪检测DC-CIK、MAGE-A3-DC-CIK的表型;流式细胞仪分选子宫内膜癌细胞系Ishikawa的CD133⁺干细胞,以子宫内膜癌干细胞作为靶细胞,分别以CIK、DC-CIK及MAGE-A3-DC-CIK作为效应细胞,MTT法检测效靶比为10∶1、20∶1、40∶1的细胞杀伤活性,ELISA法检测联合培养细胞上清液中IFN-γ、IL-2、IL-12、IL-17水平,Annexin V-FITC/PI双染法检测子宫内膜癌干细胞凋亡;建立子宫内膜癌干细胞移植瘤裸鼠模型,尾静脉注射DC-CIK或MAGE-A3-DC-CIK,观察裸鼠肿瘤生长情况,每隔2 d测量瘤体大小,21 d后取肿瘤组织,电子天平称重,HE染色观察肿瘤组织病理形态学变化,免疫组织化学染色检测肿瘤组织内Ki-67表达。结果:分离获得细...     

晚期肿瘤患者自体CIK细胞治疗及护理体会

细胞因子激活的杀伤细胞(CIK)对人体的骨髓干细胞及造血祖细胞几乎没有毒性.因此CIK细胞在过继免疫治疗中具有良好的应用前景[1,2].现将我院2002年以来运用CIK细胞治疗晚期恶性肿瘤的疗效及护理体会报道如下.     

中医药在细胞治疗中的应用现状及未来发展趋势

细胞治疗作为新兴的现代生物医学技术,促进了以精准医学和系统生物学为代表的治疗变革,也不断地与中医关于生命认识的整体观和"天人合一"的思维接近.细胞治疗为肿瘤等多种疾病的治疗提供了新的策略,但其不良反应和应用局限制约了其在临床上的广泛应用.中医药与细胞治疗联合使用,发挥协同作用,在提高细胞治疗疗效、减轻毒副作用方面已经做...     

Research progress and clinical prospect of immunocytotherapy for the treatment of hepatocellular carcinoma

As a common malignant tumor, hepatocellular carcinoma (HCC) has high fatality rate due to its strong metastasis and high degree of malignancy. Current treatment strategies adopted in clinical practice were still conventional surgery, assisted with interventional therapy, radiotherapy and chemotherapy. However these treatments have limited effects with high recurrence rate. Current research progress of immunocytotherapy has shown that tumor cells can be directly identified and killed by stimulating the immune function and enhancing the anti-tumor immunity in tumor microenvironment. Targeted immunotherapeutics have therefore become the hope of conquering cancer in the future. It can kill tumor cells without damaging the body's immune system and function, restore and strengthen the body's natural anti-tumor immune system. It can reduce the toxic side effects of radiotherapy and chemotherapy, reduce the recurrence rate and prolong the survival period of patients with HCC. Currently, the immune cells widely studied are mainly as follows: Dendritic cells (DC), Cytokine-induced killer (CIK), DC-CIK, Chimeric antigen receptor T cells (CAR-T), Tumor infiltrating lymphocyte (TIL) and Natural killer cell (NK). Immunocytotherapy is a long-term treatment method, some studies have combined traditional therapy with immunocytotherapy and achieved significant effects, providing experimental basis for the application of immunocytotherapy. However, there are still some difficulties in the clinical application of immune cells. In this article, we discuss the application of immunocytotherapy in the clinical treatment of HCC, their effectiveness either alone or in combination with conventional therapies, and how future immunocytotherapeutics can be further improved from investigations in tumour immunology.     

龙生蛭胶囊联合阿加曲班治疗急性脑梗死的临床研究

目的 探讨龙生蛭胶囊联合阿加曲班治疗急性脑梗死的临床疗效.方法 选取2019年1月—2020年4月天津市中医药大学附属南开中医院收治的急性脑梗死患者146例,随机分为对照组和治疗组,每组各73例.对照组静脉滴注阿加曲班注射液,60 mg加入生理盐水500 mL,持续24 h,3～7 d后调整为20 mg加入生理盐水10...     

多抗甲素的药理研究进展

对近 6、7年来有关多抗甲素药理的研究进展进行综述 ,主要包括 :①调整巨噬细胞功能 ;②对人天然杀伤细胞的作用机制 ;③对人淋巴细胞免疫功能的影响 ;④对淋巴因子活化的杀伤细胞增殖及杀伤活性的影响 ;⑤增强特异性细胞毒T细胞活性 ;⑥对于动物红细胞变形能力和免疫功能的影响。     

In vitro exposure of DE‐71, a penta‐PBDE mixture,on immune endpoints in bottlenose dolphins (Tursiops truncatus) and B6C3F1 mice

Polybrominated diphenyl ethers (PBDEs) are an emerging contaminant of concern with low level exposures demonstrating toxicity in laboratory animals and wildlife, although immunotoxicity studies have been limited. Bottlenose dolphin peripheral blood leukocytes (PBLs) and mouse splenocytes were exposed to environmentally relevant DE‐71 (a penta‐PBDE mixture) concentrations (0–50 µg ml^?1) in vitro. Natural killer (NK) cell activity and lymphocyte (B and T cell) proliferation were evaluated using the parallelogram approach for risk assessment. This study aimed to substantiate results from field studies with dolphins, assess the sensitivities between the mouse model and dolphins, and to evaluate risk using the parallelogram approach. In mouse cells, NK cell activity increased at in vitro doses 0.05, 0.5 and 25 µg DE‐71 ml^?1, whereas proliferation was not modulated. In dolphin cells, NK cell activity and lymphocyte proliferation was not altered after in vitro exposure. In vitro exposure of dolphin PBLs to DE‐71 showed similar results to correlative field studies; NK cell activity in mice was more sensitive to in vitro exposure than dolphins, and the parallelogram approach showed correlation with all three endpoints to predict risk in bottlenose dolphins. Copyright © 2014 John Wiley & Sons, Ltd.     

In vitro PFOS exposure on immune endpoints in bottlenose dolphins (Tursiops truncatus) and mice

Previous studies in our lab have shown that perfluorooctane sulfonate (PFOS) modulates immune function in mice and correlates with many immune parameters in bottlenose dolphins (Tursiops truncatus). In this study, bottlenose dolphin peripheral blood leukocytes (PBLs) and adult female B6C3F1 mouse splenocytes were exposed to environmentally relevant PFOS concentrations (0–5 µg ml^–1) in vitro; and natural killer (NK) cell activity and lymphocyte proliferation (T and B cell) were assessed using the parallelogram approach for risk assessment. The objectives were: to corroborate results from the correlative studies in bottlenose dolphins with in vitro PFOS exposures; to evaluate the sensitivity of the mouse model as compared with bottlenose dolphins; and to assess risk using the parallelogram approach. In mouse cells, NK cell activity was decreased at in vitro doses of 0.01, 0.5, 0.1, 0.5 and 1 µg PFOS ml^–1 and increased at 5 µg ml^–1. Additionally, B cell proliferation was not altered, but T cell proliferation was decreased at all in vitro PFOS exposures. In dolphin cells, NK cell activity and T cell proliferation were not altered by in vitro PFOS exposure, but B cell proliferation exhibited a positive association in relation to PFOS dose. Overall, the data indicates that: the in vitro exposures of bottlenose dolphin PBLs exhibited results similar to reported correlative fields studies; that mice were generally more sensitive (for these selected endpoints) than were dolphins; and that the parallelogram approach could be used two‐thirds of the time to predict the effects in bottlenose dolphins. Copyright © 2013 John Wiley & Sons, Ltd.     

消癜冲剂对小儿过敏性紫癜免疫调节作用的临床研究

目的 观察消癜冲剂治疗过敏性紫癜(HSP)急性发作期免疫学变化及临床疗效,探索临床疗效与免疫调节作用之间的关系。方法 68例随机分成两组,西药对照组(34例),西药加消癜冲剂观察组(34例),治疗前后进行IgG,IgA,IgM,C3,CD3,CD4,CD8,CD19,NK的检测,同时与30名健康儿童作对照,观察治疗前后免疫指标变化。结果 与健康对照组比较,IgA,CD19明显升高,CD3,CD4,CD8,NK下降,差异均有显著性(P＜0．05),观察组与对照组总有效率比较差异亦有显著性(P＜0．01)。结论 HSP在急性发作期存在体液免疫和细胞免疫功能的改变,免疫功能的恢复程度与治疗转归密切相关。中药治疗HSP的疗效机理亦与调节机体的免疫功能有关。     

胰胆舒胶囊联合亚胺培南西司他丁钠治疗急性重症胰腺炎的临床研究

目的 探讨胰胆舒胶囊联合亚胺培南西司他丁钠治疗急性重症胰腺炎的临床疗效.方法 选取2019年3月—2020年4月在南阳市中心医院进行治疗的86例急性重症胰腺炎患者,根据就诊顺序分为对照组(43例)和治疗组(43例).对照组静脉滴注注射用亚胺培南西司他丁钠,1.0 g/次,同0.9％氯化钠注射液100 mL配伍,每8小时...     

化疗联合立体定向放疗治疗小细胞肺癌的临床研究

目的探讨以化疗为主同期立体定向放射治疗小细胞肺癌的临床疗效。方法选择26例入本院治疗的小细胞肺癌患者,采取同期放化疗治疗。化疗方案：EP为主方案,治疗周期4～6周期。放疗采取SRT,治疗剂量3.0～4.5GY,每周6次,中位治疗剂量38.5GY。放疗介入时间：化疗开始1～2周期后,下一周期化疗前。放疗靶区：照射原发灶及明确转移灶,淋巴引流区不做预防照射。中位随访时间为24个月。结果 （1）全组患者CR率为46.2%,PR率为38.5%,SD率为15.3%,总治疗有效率为84.6%,中位生存期为17个月,1年及2年生存率分别为80.1%及38.5%。1年及2年局部无进展生存率分别为98.1%及94.2%;（2）2级急性放射肺损伤的发生率为3.8%,2级晚期放射性肺损伤的发生率为7.7%,2级急性放射性食道损伤的发生率为11.5%,2级急性血液学毒性的发生率为7.7%。结论化疗联合SRT治疗小细胞肺癌是可行的,患者的近期疗效可,毒副反应的发生率较低,值得临床应用和推广。