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用携带甲胎蛋白基因的重组腺相关病毒或癌细胞裂解物脉冲处理的树突状细胞诱导的细胞毒性T淋巴细胞反应的比较分析。

Comparative analysis of cytotoxic T lymphocyte response induced by dendritic cells pulsed with recombinant adeno-associated virus carrying α-fetoprotein gene or cancer cell lysate.

作者信息

Zhou Jun, Ma Ping, Li Jun, Song Wei

机构信息

Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Department of Opthalmology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

出版信息

Mol Med Rep. 2015 Apr;11(4):3174-80. doi: 10.3892/mmr.2014.3059. Epub 2014 Dec 8.

DOI:10.3892/mmr.2014.3059
PMID:25484119
Abstract

Hepatocellular carcinoma (HCC) is one of the most common and difficult to treat types of cancer worldwide. Antigen‑targeted immunotherapy has the potential to be a novel and effective adjuvant for use in HCC. In the present study, recombinant adeno‑associated virus carrying the α‑fetoprotein gene (rAAV/AFP) and cancer cell lysates were used to pulse antigen‑presenting dendritic cells (DCs) in order to stimulate a cytotoxic T lymphocyte (CTL) response against HCC. rAAV/AFP‑pulsed and cancer cell lysate‑pulsed DCs resulted in a mature DC phenotype with high expression of major histocompatibility complex (MHC) class I, MHC class II, CD80, CD83 and CD86 molecules. However, rAAV/AFP‑pulsed DCs exhibited superiority over cancer cell lysate‑pulsed DCs in terms of stimulating proliferation of T cells, activating T cells to secret interferon‑γ (IFN‑γ) and inducing an AFP‑specific MHC class I‑restricted CTL response. The current data suggest that pulsing of DCs using rAAV/AFP is more effective than the cancer cell lysate‑pulsing technique, and that this technique may be used for the development of immunotherapy in AFP‑positive HCC.

摘要

肝细胞癌(HCC)是全球最常见且最难治疗的癌症类型之一。抗原靶向免疫疗法有潜力成为用于HCC的新型有效辅助疗法。在本研究中,携带甲胎蛋白基因的重组腺相关病毒(rAAV/AFP)和癌细胞裂解物被用于脉冲抗原呈递树突状细胞(DC),以刺激针对HCC的细胞毒性T淋巴细胞(CTL)反应。rAAV/AFP脉冲DC和癌细胞裂解物脉冲DC导致成熟的DC表型,主要组织相容性复合体(MHC)I类、MHC II类、CD80、CD83和CD86分子高表达。然而,在刺激T细胞增殖、激活T细胞分泌干扰素-γ(IFN-γ)以及诱导甲胎蛋白特异性MHC I类限制性CTL反应方面,rAAV/AFP脉冲DC比癌细胞裂解物脉冲DC表现出优势。当前数据表明,使用rAAV/AFP脉冲DC比癌细胞裂解物脉冲技术更有效,且该技术可用于甲胎蛋白阳性HCC免疫疗法的开发。

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