《新英格兰医学杂志》报道：大获成功的白血病的基因打靶疗法

一般癌细胞表面都有生物标记。慢性淋巴细胞性白血病（CLL）大都是B细胞，CD19是B细胞的表面抗原。新的基因打靶疗法是让病人的T淋巴细胞通过转基因技术，产生anti-CD19的混合抗原受体（Chimeric antigen receptors），这样用转基因技术处理后的患者的T细胞就能针对性地袭击B细胞CLL，从而达到歼灭癌细胞的效果。这是一个最新的抗癌概念和技术，所以没有任何Grant赞助。

第一批三位CLL病人的临床试验是在私人赞助下完成的。结果是大满贯，三个病人的癌细胞都消失了。这个结果让人看到了新一代抗癌疗法的希望，周三的文章发表后，许多机构和药厂都纷纷前来投资这个新的抗癌研究项目。。。

A small group of patients with an advanced form of tough-to-treat leukemia appears to have benefited from a radical new form of immune therapy, researchers say.

To treat chronic lymphocytic leukemia (CLL) that had not responded to other therapies, scientists inserted a genetically modified version of the patients' own T cells (immune cells) into three patients to specifically target the CLL cells. Almost a year later, the patients are in complete or partial remission.

This is the first time scientists have successfully used gene transfer therapy to kill cancer cells, and the results might be applicable to other forms of cancer, including ovarian and lung tumors, the researchers said.

"This approach to adaptive therapy with T cells is different and better [than previous immunotherapy attempts] because the cells are long-lived once they're transferred and active over a period of time," said William Chambers, director of the Clinical Cancer Research and Immunology Program at the American Cancer Society. "And it seems that a small number of them actually have a big impact," he noted. "This is going to prove useful and important."

The challenge now is to find the right target on other cancers, he added.

The researchers, who presented their findings Aug. 10 in the New England Journal of Medicine and Science Translational Medicine, removed the patients' own T cells and then added an artificial receptor that specifically targeted CD19, a protein found on these types of cancer cells.

These engineered T cells, which were re-introduced after chemotherapy, also were programmed to produce even more killer cells.

"This turned every genetically modified T cell into a tumor-seeking missile," explained Bruce Levine, co-author of both papers and associate professor of pathology and laboratory medicine at the University of Pennsylvania's Abramson Cancer Center in Philadelphia.

In the case of a 64-year-old man, whose experience is chronicled in the NEJM article, T cells started killing tumor cells within two weeks of the first treatment.

Four weeks out, he showed no evidence of leukemia at all.

All the patients are now 10, 11 and 12 months out from treatment.

The gene-modified T cells destroyed about two pounds of tumor in each patient in about a month. One T cell was able to kill about 1,000 cancer cells, the authors said.

"The results were quite striking considering that each of these patients had been undergoing the best conventional medicine could give," said Levine. "When you look at the responses these patients achieved and the time frame in which they achieved them, it's extraordinarily remarkable."

Chambers was impressed that the T cells were active for as long as six months.

"That's important because a cancer like this can go all through the body and be hidden in different places," he said. "One would presume that you wouldn't have to go back and do a bunch of continuing treatments."

But there was one downside to treatment, Chambers said. In one patient, normal immune cells were also affected.

CLL, which typically strikes in middle age, is diagnosed in almost 15,000 men and women in the United States each year, according to the U.S. National Cancer Institute. More than 4,000 adults die of it a year. Current treatments include chemotherapy, bone marrow transplants and biologics (such as rituximab).

For now, the new treatment is only available for patients in clinical trials for leukemia and lymphoma, and the researchers need to get a longer-term view before it can be recommended for broader use.

Their next step is to try the approach in patients who have other CD19-positive tumors, such as non-Hodgkin lymphoma and acute lymphocytic leukemia, and in children who don't respond to conventional treatments for pediatric leukemia.

REF：David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D. Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. New England Journal of Medicine  August 10, 2011 (10.1056/NEJMoa1103849)