Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells

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Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade

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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100 mL,持续2~3 h,2次/d。治疗组患者在对照组的基础上,口服龙生蛭胶囊治疗,5粒/次,疗程为2周。观察两组患者临床疗效,比较治疗前后两组患者生活质量、神经功能缺损评分(NIHSS)、Barthel指数(BI)评分、颈动脉斑块,及钙调素(CAM)、肿瘤坏死因子-α(TNF-α)、正五聚体蛋白-3(PTX-3)、生长分化因子-15(GDF-15)和白细胞介素-6(1L-6)水平。结果治疗后,治疗组的总有效率为93.15%,明显高于对照组的79.45%(P<0.05)。治疗后,两组生理功能、情感功能和社会功能评分较治疗前的明显升高(P<0.05),治疗组升高更明显(P<0.05)。两组患者在治疗的第7天、第14天,NIHSS评分与BI评分较治疗前明显改善(P<0.05),治疗组在治疗的第14天,NIHSS评分与BI评分明显好于对照组(P<0.05);与对照组相比,治疗组IMT厚度和斑块面积降低更为显著(P<0.05)。治疗后,两组CAM、TNF-α、PTX-3、GDF-15和1L-6水平较治疗前显著降低(P<0.05),而且与对照组相比,治疗组下降更为明显(P<0.05)。结论龙生蛭胶囊联合阿加曲班治疗急性脑梗死效果显著,能够有效的提高患者的生活质量,降低神经功能缺损的严重程度和斑块面积,有效的改善临床指标。     

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.     

CAR-T细胞免疫疗法的研究进展

 嵌合抗原受体T细胞（chimeric antigen receptor T-cell,CAR-T）免疫治疗可以精准靶向癌细胞,在肿瘤（尤其是淋巴瘤）的临床治疗上表现出良好的效果,是近年来受到广泛关注的一种肿瘤免疫治疗方法。目前CAR-T在淋巴瘤中的应用趋于成熟,但在实体瘤中由于肿瘤微环境等因素导致CAR-T疗法应用受限。本文概述了当前CAR-T免疫疗法面临的挑战及相关机制研究,如靶向肿瘤的特异性、安全性以及CAR-T的持久性等,同时聚焦针对这些挑战对CAR-T的CAR结构设计进行优化的研究进展。     

CAR-T治疗难治/复发B细胞肿瘤患者后继发第二肿瘤2例并文献复习

目的分析基于嵌合抗原受体修饰的T细胞(chimeric antigen receptors-modified T cells,CAR-T)疗法在难治/复发B细胞肿瘤患者治疗中的临床特点及疗效。方法回顾分析2例B细胞肿瘤患者接受CAR-T治疗后继发第二肿瘤的病例资料并复习相关文献。结果1例诊断为滤泡性淋巴瘤,接受CD19及CD22 CAR-T治疗后,无进展生存期为28个月,后继发腺癌;1例诊断为急性B淋巴细胞白血病,接受CD19 CAR-T治疗后,无进展生存期为14个月,后继发急性髓系白血病。结论CAR-T治疗在B细胞肿瘤患者治疗中取得巨大突破,但这一疗法在临床应用中仍存在诱发第二肿瘤等远期不良反应,在临床实践中需要长期随访与总结。     

重组人促血小板生成素在多发性骨髓瘤患者自体外周血干细胞移植中的临床应用

目的探讨重组人促血小板生成素(recombinant human thrombopoietin,rhTPO)在多发性骨髓瘤(multiple myeloma,MM)患者自体外周血干细胞移植(autologous peripheral blood stem cell transplantation,APBSCT)中的临床价值。方法分析2010年1月至2019年12月本中心收集的CD34+自体造血干细胞数目低于2×10^(6)/kg(患者体重)并完成APBSCT的MM患者的临床资料,比较单用粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)及G-CSF联合rhTPO在APBSCT中促进骨髓造血重建的差异。结果根据APBSCT期间应用造血生长因子的不同,将患者分为G-CSF组(n=39)和G-CSF+rhTPO组(n=53)。两组患者平均CD34+干细胞数量差异无统计学意义(P=0.149),G-CSF+rhTPO组中性粒细胞植入平均时间较G-CSF组缩短[(11.21±1.03)d vs(12.13±1.47)d,P=0.001],血小板植入速度较G-CSF组快[(12.66±2.35)d vs(15.36±5.79)d,P=0.008],平均血小板输注治疗量低于G-CSF组[(1.79±0.77)个治疗量vs(2.46±1.82)个治疗量,P=0.036],总体感染率和3~4级感染率也较G-CSF组低(34.0%vs 41.0%,P=0.041;5.7%vs 23.1%,P=0.001)。结论rhTPO在MM患者APBSCT中起重要作用,与G-CSF联合能加速骨髓造血重建,降低血小板输注量和严重感染发生率。