慢性乙型肝炎的新型免疫细胞疗法

StephenW

慢性乙型肝炎的新型免疫细胞疗法更新时间：2013-5-28    作者：佚名    文章来源：国际肝病网

　　强有效的T细胞应答是清除HBV所不可或缺的，但这也恰好是慢性乙型肝炎患者所欠缺的。德国慕尼黑工业大学病毒研究所Krebs等尝试将T细胞导向于病毒感染细胞以清除病毒，并在动物实验中取得了初步成功。
　　Krebs的方法是在体外通过逆转录载体使CD8+T细胞表达能与HBV包膜蛋白结合的嵌合抗原受体（S-CAR），随后将表达S-CAR的CD8+T细胞被动转入HBV转基因小鼠体内。结果显示，表达S-CAR的CD8+T细胞能识别多种HBV亚型，能被成功植入免疫健全的HBV转基因小鼠，并在小鼠体内扩增。这些T细胞主要定位于肝脏，并在肝内发挥功能，能迅速有效地控制HBV复制，仅引起一过性肝损伤。
　　该研究提示，循环中的大量病毒抗原并不削弱或过度活化这些植入的表达S-CAR的CD8+T细胞。这种免疫细胞疗法不受人白细胞抗原限制，可加以开发用于人类。

StephenW

Gastroenterology. 2013 Apr 29. pii: S0016-5085(13)00684-7. doi: 10.1053/j.gastro.2013.04.047. [Epub ahead of print]
T Cells Expressing a Chimeric Antigen Receptor That Binds Hepatitis B Virus Envelop Proteins Control Virus Replication in Mice.Krebs K, Böttinger N, Huang LR, Chmielewski M, Arzberger S, Gasteiger G, Jäger C, Schmitt E, Bohne F, Aichler M, Uckert W, Abken H, Heikenwalder M, Knolle P, Protzer U.
SourceInstitute of Virology, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.

AbstractBACKGROUND & AIMS: Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors, and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft following adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled, immune-mediated damage.
METHODS: CD8+ T cells were isolated from mice and stimulated using an optimized protocol. Chimeric antigen receptors (CARs) that bind HBV envelope proteins (S-CAR) and activate T cells were expressed on the surface of cells using retroviral vectors. S-CAR-expressing CD8+ T cells, which carried the marker CD45.1, were injected into CD45.2+ HBV transgenic mice. We compared these mice with mice that received CD8+ T cells induced by vaccination, cells that express a CAR without a proper signaling domain, or cells that express a CAR that does not bind HBV proteins (controls).
RESULTS: CD8+ T cells that expressed HBV-specific CARs recognized different HBV subtypes and were able to engraft and expand in immune-competent HBV transgenic mice. Following adoptive transfer, the S-CAR-expressing T cells localized to and functioned in the liver; they rapidly and efficiently controlled HBV replication, compared with controls, causing only transient liver damage. The large amount of circulating viral antigen did not impair or over-activate the S-CAR grafted T cells.
CONCLUSION: T cells with a CAR specific for HBV envelop proteins localize to the livers of mice to reduce HBV replication, causing only transient liver damage. This immune-cell therapy might be developed for patients with chronic hepatitis B, regardless of their HLA-type.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

卡奥卡

“这些T细胞主要定位于肝脏，并在肝内发挥功能，能迅速有效地控制HBV复制”。这种疗法和核苷的作用一样吗？只能控制复制，不能完全杀灭CCCDNA？

sddp1

回复 卡奥卡 的帖子

疗效还有待观察吧，不过从提高或激活自己免疫的方面来控制hbv的感染，比仅仅依靠核苷又多了种方法。让人想起了多年前的自体lak细胞回输治疗CHB

StephenW

回复 卡奥卡 的帖子

我不完全了解 T细胞免疫.
一般来说, CD8 + T细胞控制病毒：
1。通过杀死被感染的细胞（因此清除细胞内cccDNA）
2。不杀死感染的细胞，但控制/清除
细胞内cccDNA（怎么样，我不知道）

如sddp1说, 它是细胞回输治疗, 成为治疗要走很长的路.