《新英格蘭醫學雜誌》報道：大獲成功的白血病的基因打靶療法

一般癌細胞表麵都有生物標記。慢性淋巴細胞性白血病（CLL）大都是B細胞，CD19是B細胞的表麵抗原。新的基因打靶療法是讓病人的T淋巴細胞通過轉基因技術，產生anti-CD19的混合抗原受體（Chimeric antigen receptors），這樣用轉基因技術處理後的患者的T細胞就能針對性地襲擊B細胞CLL，從而達到殲滅癌細胞的效果。這是一個最新的抗癌概念和技術，所以沒有任何Grant讚助。

第一批三位CLL病人的臨床試驗是在私人讚助下完成的。結果是大滿貫，三個病人的癌細胞都消失了。這個結果讓人看到了新一代抗癌療法的希望，周三的文章發表後，許多機構和藥廠都紛紛前來投資這個新的抗癌研究項目。。。

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)