免疫新技术：植入物鼓动细胞大军攻击癌细胞或病毒

brucexm

Article abstractNature Materials
Published online: 11 January 2009 | doi:10.1038/nmat2357

Infection-mimicking materials to program dendritic cells in situOmar A. Ali1, Nathaniel Huebsch1,2, Lan Cao1, Glenn Dranoff3 & David J. Mooney1,4,5

AbstractCancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25 days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body.

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School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02138, USA Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA
• Present address: Harvard School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., 319 Pierce Hall, Cambridge, Massachusetts 02138, USA

Correspondence to: David J. Mooney1,4,5 e-mail: [email protected]



由于癌细胞来自身体内部，因此人体免疫系统通常是不问不管。现有的疗法是取出免疫细胞，对其重新编程，使其能攻击恶性组织，然后再移植回去。但是这种方法的疗效并不令人鼓舞，因为超过90%的重新注入的细胞在生效之前就已死去。

现在哈佛大学教授David Mooney和同事开发出一种新技术，通过植入物直接对身体内的免疫细胞编程，去攻击传染病甚至癌症。对带有恶性黑素瘤的老鼠试验显示，癌细胞在25天内就被清除，新的疗法更高效也更廉价。 这项突破技术的原理是：向人体植入一种FDA批准的生物降解聚合物圆筒，植入物释放出称作cytokines的细胞信号分子——一种能诱使免疫系统信使细胞的分子香精。这些树状细胞聚合到植入物周围，就像警犬一样被抗原熏陶，所谓抗原是被免疫系统看作异体，因此引起免疫反应的分子。这些抗原包含了癌细胞、细菌或病毒分子的签名。然后树状细胞闻到警告信号离去，碰到免疫系统手下的杀手“T细胞”后就会对其编程，令其穷追不舍的杀死癌细胞或病毒。 论文发表在最新一期的《自然材料学》杂志上

[ 本帖最后由 brucexm 于 2009-1-17 16:59 编辑 ]

战斗胜佛

就像看科幻.

614

星球大战.........

春波

不要不相信  美利坚合众国总是很强悍  不是我崇洋媚外  那里是世界上最优秀人才聚集地  很多人的梦想在那里实现

marsq

好兴奋！
作为一个HBV患者，我一直有个想法：能否给被病毒寄生的细胞打上一个标签，让免疫系统识别，然后清除！
事实证明，我的想法并非天马行空，并非痴人说梦话！
期待！

特深沉

我喜欢看一类真人和动画联合一起的电影。比如经典的Who Framed Roger Rabbit.
其实我想推荐的是另外一个片子： Osmosis

[ 本帖最后由 特深沉 于 2009-1-18 14:13 编辑 ]

lazio13

未来10年没有可能

索母河磐石

普及最关键

特深沉

http://www.technologyreview.com/biomedicine/22027/

Wednesday, January 28, 2009

Implant Makes Cells Kill Cancer

A polymer device trains immune cells to shrink tumors

One of cancer's cleverest tricks is its ability to hide from the immune system. A new approach to cancer treatment called immunotherapy could spare patients at least some of the grueling battery of chemotherapy treatments by retraining the body's own defenders--the cells of the immune system--to recognize and destroy tumors. Now researchers at Harvard University have developed a simple way to do this inside the body: a polymer implant attracts and trains immune-system cells to go after cancer.

The experimental approach has shown great success in animal studies, increasing the survival rate of mice with a deadly melanoma from 0 to 90 percent. The implant could also be used to treat diseases of the immune system such as arthritis and diabetes, and, potentially, to train other kinds of cells, including stem cells used to repair damage to the body.

The usual methods for cancer immunotherapy are complex and have had little success in clinical trials, says David Mooney, a professor of bioengineering at Harvard who leads the development of the implant. First, immune cells called dendritic cells are removed from a patient's body; then they're exposed to chemical activators and cancer-specific antigens. These cells are then injected back into the patient, where they should, in theory, travel to the lymph nodes and activate another group of cells called T cells, training them to attack a tumor. But dendritic cells are fragile, and while this approach has increased survival in mice, it hasn't caused tumors to shrink in clinical trials with humans.

"When you transplant the cells, virtually all of them die, and you have very little control over what they do when they're reimplanted," says Mooney. So his team took a different approach to the problem, realizing that "perhaps we could do all this inside the body."

Mooney and his research group constructed a polymer that can do inside the body what complex immunotherapies do outside it. They describe the design and performance of an implant for melanoma in the current issue of Nature Materials. The polymer has a history of safe use in humans (in biodegradable sutures, for example). First, it attracts dendritic cells by releasing a kind of chemical signal called a cytokine. Once the cells are there, they take up temporary residence inside spongelike holes within the polymer, allowing time for the cells to become highly active.

The polymer carries two signals that serve to activate dendritic cells. In addition to displaying cancer-specific antigens to train the dendritic cells, it is also covered with fragments of DNA, the sequence of which is typical of bacteria. When cells grab on to these fragments, they become highly activated. "This makes the cells think they're in the midst of infection," Mooney explains. "Frequently, the things you can do to cells are transient--especially in cancer, where tumors prevent the immune system from generating a strong response." This extra irritant was necessary to generate a strong response, the Harvard researchers found.

When implanted just under the skin of mice carrying a deadly form of melanoma, the polymer increased their survival rate to about 90 percent. By contrast, conventional immunotherapies that require treating the cells outside the body are 60 percent effective, says Mooney.

特深沉

Robert Langer, a pioneer in developing drug-delivering polymers and an Institute Professor at MIT, says that Mooney's work is "a really beautiful combination of materials science and cell technology."

Accomplishing the entire immunotherapeutic process inside the body using a common polymer is "incredible," adds Peter Polverini, dean of dentistry and a professor of pathology at the University of Michigan, and a specialist in oral cancer. "From the standpoint of efficacy and efficiency, this is a huge advance." For patients, he says, a subcutaneous implant would be "far less burdensome" than doctors removing and reimplanting cells.

Mooney developed the polymer systems with more than melanoma in mind, however. He hopes to develop similar implants for treating other types of cancer, which should simply be a matter of changing the antigen carried by the polymer. But the approach could also be used to treat other kinds of immune disorders. For example, different chemical signals could dampen immune cells' activity in order to prevent transplant rejections and treat autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, which result when the immune system attacks normal tissues. Mooney also hopes that the polymer system can train a different class of cells altogether. Just as fragile dendritic cells seem to respond better to being trained inside the body, this might be a more effective way to recruit and reprogram stem cells.

If proved in people, the cell-training polymers might also bypass some of the regulatory hurdles and expense faced by cell therapies, since devices are more readily approved by the Food and Drug Administration. Indeed, Mooney predicts that the therapy will move quickly through safety tests in large animals (the next step before human trials), and he expects to bring the cancer immunotherapy to clinical trials soon. "All the components are widely used and tested, and shown to be safe," he says.

One thing that remains to be proved, however, is whether the treatment is effective over the long term--whether the body will recognize the cancer cells months and even years later, after the polymer has biodegraded. Most cancer deaths are caused by secondary tumors called metastases that can arise from just a single cell that leaves the primary tumor. The immune system's ability to remember disease-causing agents over the long term is one of the reasons that immunotherapy for cancer seems so promising. Once the cells have been trained to recognize and attack a tumor, the immune system should be prepared to combat cancer recurrence. Mooney says that he's currently working on long-term studies. "Just think what the benefit would be to patients to have their immune system reprogrammed at will to fight disease in a sustained fashion," says Polverini.