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α1,3-半乳糖基化表位修饰的树突状细胞与细胞因子诱导的杀伤细胞联合用于肝癌的特异性免疫治疗。

Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells.

机构信息

The First Teaching Hospital, Inner Mongolia Medical College, Huhhot 010050, Inner Mongolia Autonomous Region, China.

出版信息

World J Gastroenterol. 2011 Dec 28;17(48):5260-6. doi: 10.3748/wjg.v17.i48.5260.

Abstract

AIM

To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.

METHODS

Freshly collected hepatocellular carcinoma (HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage III primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.

RESULTS

The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo, P = 0.00121). After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.

CONCLUSION

This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.

摘要

目的

评估使用α-Gal 表位脉冲树突状细胞(DC)和细胞因子诱导的杀伤细胞的新型免疫疗法的安全性和临床疗效。

方法

新鲜收集的肝细胞癌(HCC)肿瘤组织与神经氨酸酶和重组α1,3-半乳糖基转移酶(α1,3GT)混合物孵育,以在肿瘤膜糖蛋白的碳水化合物链上合成α-Gal 表位。随后,在存在人天然抗-Gal IgG 的情况下孵育处理过的膜,导致 DC 有效吞噬肿瘤膜。18 名年龄 38-78 岁的 III 期原发性 HCC 患者被随机选择进行研究;9 名患者作为对照组,9 名患者纳入研究组。

结果

评估表明该程序是安全的;未观察到严重的副作用或自身免疫性疾病。与对照组相比,该疗法显著延长了治疗患者的生存期(17.1 ± 2.01 个月 vs 10.1 ± 4.5 个月,P = 0.00121)。治疗后,研究组所有患者均对肿瘤裂解物产生阳性迟发型超敏反应和强大的全身细胞毒性,这可通过酶联免疫斑点法检测外周血单个核细胞中干扰素-γ表达来衡量。他们还显示外周血中 CD8+、CD45RO+和 CD56+阳性细胞数量增加,血清中甲胎蛋白水平降低。

结论

这种新的肿瘤特异性免疫疗法安全、有效,具有治疗肿瘤的巨大潜力。

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