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海外医疗:脊髓灰质炎病毒可以杀死癌细胞,阻止肿瘤再生

王彦 发布于 2018-02-02 18:14:19

来自北卡罗来纳州达勒姆的杜克大学的研究人员们可能发现了一种杀死癌细胞的新方法。

该团队由神经外科系的教授Matthias Gromeier博士和外科学系的免疫学家Smita Nair教授共同领导。

这项新研究发表在《科学转化医学》杂志上,它展示了修改过的脊髓灰质炎病毒是如何使人体利用自己的资源对抗癌症的。该修改后的病毒用重组肿瘤脊髓灰质炎病毒(PVS-RIPO)命名。

修改过的脊髓灰质炎病毒可以使T细胞攻击癌细胞(如图所示)。

自2011年以来,一直在进行重组肿瘤脊髓灰质炎病毒(PVS-RIPO)的临床试验,初步的结果给患有危险的脑瘤之一的复发性胶质母细胞瘤患者带来了治疗的希望。因此,研究人员开始深入调查重组肿瘤脊髓灰质炎病毒(PVS-RIPO)到底是如何工作的。

Gromeier博士解释了他们的研究原理,他说 “知道产生免疫反应的步骤,这将使我们能够理性地决定是否使用其他疗法和使用什么样的疗法与脊髓灰质炎病毒结合在一起,用来治疗病人和改善病人的状况。”

研究人员在两种人类细胞系中研究了脊髓灰质炎病毒的行为,分别是黑素瘤和三阴性乳腺癌。他们观察到脊髓灰质炎病毒附着在癌细胞上。这些细胞有过量的CD155蛋白,这是脊髓灰质炎病毒的受体。

然后,脊髓灰质炎病毒开始攻击恶性细胞,刺激肿瘤使其释放出抗原。抗原是人体无法识别的有毒物质,因此人体会对其产生免疫攻击。

所以,当肿瘤细胞释放抗原时,就会提醒机体的免疫系统开始攻击。与此同时,脊髓灰质炎病毒感染树突细胞和巨噬细胞。

树突状细胞是那些处理抗原并将其“呈现”到T细胞中(T细胞是一种免疫细胞)的细胞们。巨噬细胞是另一种免疫细胞,即大的白细胞,它的主要作用是清除我们体内的碎片和有毒物质。

研究人员们随后在小鼠模型中进行验证,细胞培养的结果显示一旦重组肿瘤脊髓灰质炎病毒(PVS-RIPO)感染了树突细胞,这些细胞就会“告诉”T细胞开始免疫攻击。

一旦免疫攻击开始,这个过程似乎是持续成功的。癌细胞在较长一段时间内仍然容易受到免疫系统的攻击,这似乎阻止了肿瘤的再生长。

正如Nair教授所解释的,“不仅是脊髓灰质炎病毒杀死肿瘤细胞,它还感染了抗原呈递细胞,使它们能够以这样一种方式发挥作用,从而提高T细胞的反应,进而识别和渗透肿瘤。”

“这是一个令人鼓舞的新发现,因为它意味着脊髓灰质炎病毒可以刺激自身的炎症反应。”

---- Smita Nair教授

Gromeier博士在《今日医学新闻》中谈到了这一发现的临床意义以及科学家未来研究的方向,他说:“我们的研究结果为推进乳腺癌、前列腺癌和恶性黑色素瘤的临床试验提供了明确的方向。”

他补充说:“这包括我们将继续研究的新型组合疗方法。“

他更具体地解释说,因为研究表明,在髓灰质炎病毒治疗后,“免疫细胞会增加免疫检查点,“研究人员规划的未来的计划是“将(肿瘤细胞)脊髓灰质炎病毒和免疫检查点结合。”

来源:今日医学新闻

作者:Ana Sandoiu

翻译:麻省医疗国际左文超

Poliovirus kills off cancer cells, stops tumor regrowth

Published Today

By Ana Sandoiu

The modified poliovirus appears to enable T cells to attack cancer cells (shown here).

Researchers from Duke University in Durham, NC, may have discovered a new way of killing off cancer cells.

The team was jointly led by Dr. Matthias Gromeier, a professor in the Department of Neurosurgery, and Prof. Smita Nair, who is an immunologist in the Department of Surgery.

The new research - which is published in the journal Science Translational Medicine - shows how a modified poliovirus enables the body to use its own resources to fight off cancer. The modified virus bears the name of recombinant oncolytic poliovirus (PVS-RIPO).

PVS-RIPO has been in clinical trials since 2011 and preliminary results have offered hope to patients with one of the most aggressive forms of brain tumor: recurrent glioblastoma. So, the researchers set out to investigate more deeply how exactly PVS-RIPO works.

Explaining the rationale behind their research endeavor, Dr. Gromeier says, "Knowing the steps that occur to generate an immune response will enable us to rationally decide whether and what other therapies make sense in combination with poliovirus to improve patient survival."

Poliovirus attacks tumors, inhibits regrowth

The researchers examined the behavior of the poliovirus in two human cell lines: melanoma and triple-negative breast cancer. They observed that the poliovirus attaches itself to cancerous cells. These cells have an excess of the CD155 protein, which acts as a receptor for the poliovirus.

Then, the poliovirus starts to attack the malignant cells, triggering the release of antigens from thetumor. Antigens are toxic substances that the body does not recognize, therefore setting off an immune attack against them.

So, when the tumor cells release antigens, this alerts the body's immune system to start attacking. At the same time, the poliovirus infects the dendritic cells and macrophages.

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Dendritic cells are cells whose role it is to process antigens and "present" them to T cells, which are a type of immune cell. Macrophages are another type of immune cell - namely, large white blood cells whose main role is to rid our bodies of debris and toxic substances.

The cell culture results - which the researchers then verified in mouse models - showed that once PVS-RIPO infects the dendritic cells, these cells "tell" T cells to start the immune attack.

Once started, this process seems to be continuously successful. The cancer cells continue to be vulnerable to the immune system's attack over a longer period of time, which appears to stop the tumor from regrowing.

As Prof. Nair explains, "Not only is poliovirus killing tumor cells, it is also infecting the antigen-presenting cells, which allows them to function in such a way that they can now raise a T cell response that can recognize and infiltrate a tumor."

"This is an encouraging finding, because it means the poliovirus stimulates an innate inflammatory response."

Prof. Smita Nair

Speaking to Medical News Today about the clinical implications of the findings and the scientists' directions for future research, Dr. Gromeier said, "Our findings provide clear rationales for moving forward with clinical trials in breast cancer, prostate cancer, and malignant melanoma."

"This includes novel combination treatments that we will pursue," he added.

More specifically, he explains, because the study revealed that after treatment with the poliovirus "immune checkpoints are increased on immune cells," a future strategy the researchers plan to explore is "[oncolytic] poliovirus combined with immune checkpoint blockade."

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