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[针对肝细胞癌的细胞毒性T淋巴细胞的实验与临床研究]

[Experimental and clinical research of cytolytic T lymphocytes specific for hepatocellular carcinoma].

作者信息

Shen F, Wang H, Xie T

机构信息

Second Military Medical University, Shanghai Oreintal Hepatobiliary Surgery Hospital.

出版信息

Zhonghua Wai Ke Za Zhi. 1997 Feb;35(2):95-9.

Abstract

To investigate a new kind of anti-tumor immunological cells and improve surgical results of hepatocellular carcinoma by anti-recurrence application, we activated T cells isolated from tumor infiltrating lymphocytes by double stimulating signals: the one was autologus HCC cells which were treated with IFN-gamma and TNF-alpha for enhancing expression of MHC class I and presented tumor antigen, and the other was costimulation signals which was from ICAM-1 and B7 molecules expressed on treated HCC cells as well as CD28 mAbs. Activated T cells which bound to HCC cells were expanded selectively as tumor specific cytotoxic T lymphocytes (TS-CTLs), their cytotoxic activity in vitro and anti-tumor effects in vivo were observed. Our results suggested that TS-CTLs expressed high cytotoxicity against autologous HCC cells with MHC class I restriction manner. Adoptive TS-CTLs treatment could decrease serum AFP level, inhibit ascites formation and prolong survival in SCID mice bearing human HCC. In clinical trail of 12 cases of HCC, TS-CTLs treatment was able to delay tumor recurrence after HCC resection. Our data demonstrated that TS-CTLs as new immunological treatment modality, are of great value in further application of tumor comprehensive management.

摘要

为研究一种新型抗肿瘤免疫细胞,并通过抗复发应用提高肝细胞癌的手术疗效,我们利用双重刺激信号激活从肿瘤浸润淋巴细胞中分离出的T细胞:一种是经干扰素-γ和肿瘤坏死因子-α处理以增强MHC I类表达并呈递肿瘤抗原的自体肝癌细胞,另一种是来自经处理的肝癌细胞上表达的细胞间黏附分子-1和B7分子以及CD28单克隆抗体的共刺激信号。与肝癌细胞结合的活化T细胞作为肿瘤特异性细胞毒性T淋巴细胞(TS-CTLs)被选择性扩增,观察其体外细胞毒性活性和体内抗肿瘤作用。我们的结果表明,TS-CTLs以MHC I类限制方式对自体肝癌细胞表现出高细胞毒性。过继性TS-CTLs治疗可降低荷人肝癌SCID小鼠的血清甲胎蛋白水平,抑制腹水形成并延长生存期。在12例肝癌的临床试验中,TS-CTLs治疗能够延迟肝癌切除术后的肿瘤复发。我们的数据表明,TS-CTLs作为一种新的免疫治疗方式,在肿瘤综合治疗的进一步应用中具有重要价值。

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