２013年12月份第342期的國際知名SCIENCE雜誌中，刊載了有關免疫療法的運作機制和成效，有實際的數據證實。可以見得免疫療法做為癌症治療，對癌症患者來說，是正規治療之外的一大福音。

 

SCIENCE雜誌網站資訊如下：
http://www.sciencemag.org/content/342/6165/1432.full%E2%80%8D

 

全文內容：

 

Cancer Immunotherapy

 

This year marks a turning point in cancer, as long-sought efforts to unleash the immune system against tumors are paying off—even if the future remains a question mark.

 

　History’s path is unchartable when it’s not yet past but present, when we are still standing in the middle of it.That’s what madeScience’s selection of this year’s Breakthrough of the Year such a topic of internal debate, even anxiety.In celebrating cancer immunotherapy—harnessing the immune system to battle tumors—did we risk hyping an approachwhose ultimate impact remains unknown? Were we irresponsible to label as abreakthrough a strategy that has touched a tiny fraction of cancer patients andhelped only some of them? What do we mean when we call something abreakthrough, anyway?

 

　Ultimately, we concluded, cancer immunotherapy passes the test. It does sobecause this year, clinical trials have cemented its potential in patients andswayed even the skeptics. The fi eld hums with stories of lives extended:thewoman with a grapefruit-size tumor in her lung from melanoma, alive and healthy13 years later; the 6-yearold near death from leukemia, now in third grade andin remission; the man with metastatic kidney cancer whose disease continuedfading away even after treatment stopped.

 

　As the anecdotes coalesce into data, there’s another layer, too, a sense ofparadigms shifting.Immunotherapy marks an entirely different way of treating cancer—by targeting theimmune system, not thetumor itself. Oncologists,a grounded-in-reality bunch,say a corner has been turned and we won’t be going back.

 

　With much pressure these days to transform biological insights intolifesaving drugs, there’s a lesson to be learned from immunotherapy’s successes: They emerged from acareful decoding of basic biology that spanned many years. The early steps weretaken by cancer immunologist James Allison, now at the University of Texas MDAnderson Cancer Center in Houston. In the late 1980s,French researchers whoweren’t thinking aboutcancer at all identifi ed a new protein receptor on the surface of T cells,called cytotoxic T-lymphocyte antigen 4, or CTLA-4. Allison found that CTLA-4puts the brakes on T cells, preventing them from launching full-out immuneattacks. He wondered whether blocking the blocker—the CTLA-4 molecule—would set theimmune system free to destroy cancer.

 

　Allison’s rationale was untested. He and his colleagues changed the conversation,in the words of one cancer researcher,“to consider immunosuppression as the focal point, and manipulation ofimmunosuppression as the target.”

 

　Doing so took time. CTLA-4 was discovered in 1987. In 1996, Allisonpublished a paper in Science showing that antibodies against CTLA-4 erasedtumors in mice.

 

　Pharmaceuticalcompanies shied away from cancer　immunotherapy, wary of past fl ops butalso of a strategy very　unlike the standard zapping of a tumor. So the job ofgetting　anti–CTLA-4 into people fell to a small biotechnology　company, Medarex, inPrinceton, New Jersey. In 1999, it　acquired rights to the antibody, takingthe leap from biology　to drug.

 

　Crucial results didn’t come for another 11years. In 2010,　Bristol-Myers Squibb—which had boughtMedarex for　more than $2 billion—reported that patients with metastatic　melanoma lived anaverage of 10 months on the antibody,　compared with 6 months without it. It wasthe fi rst time　any treatment hadextended life in advanced melanoma in　a randomized trial. Nearly a quarter ofparticipants survived at least 2 years.

 

　The numbers foranother antibody are so far even better and the side effects milder. In the early 1990s, abiologist in Japan discovered a molecule expressed in dying Tcells, which he called programmed death 1, or PD-1, and which he recognized as another brake on T cells. He wasn’t thinking of cancer, but others did. One, oncologist Drew Pardollat Johns Hopkins University, met with a leader of Medarex ata Baltimore coffee shop. He urged the company to test ananti–PD-1 antibody in people.

 

　The first trial,with 39 patients and fi ve different cancers, began in 2006. By 2008, doctors were jolted by what they saw: In fi ve of the volunteers, all of them withrefractory disease, tumors were shrinking. Survival in a few stretched beyond what was imagined possible.

 

　Still, understandingwhat these therapies were doing inside the body was a challenge. Other cancer treatments either work or they don’t, and the answer is nearlyinstantaneous. With both anti–CTLA-4 and anti–PD-1, physicians saw some tumors grow before vanishing months later. Some patients kept responding even after the antibody had been discontinued, suggesting their immune system had been

fundamentallychanged. Some, particularly those on anti–CTLA-4, developedunnerving side effects, infl ammation of the colon, for example, or of the pituitary gland. All ofthese were the fi ne points of a new template, one whosevagaries physicians were just beginning to understand. Thelearning curve would be steep.

 

　It was steep inanother area of immunotherapy as well. For years, Steven Rosenberg at the National Cancer Institutehad harvested T cells that had migrated into tumors, expanded them in the lab, and reinfused them into patients, saving some with dire prognoses. The technique worked only when doctors could access tumor tissue, though, limitingits application.

 

　Then in 2010,Rosenberg published encouraging results from so-called chimeric antigen receptor therapy, or CAR therapy—a personalizedtreatment that involves geneticallymodifying a patient’sT cells to make them target tumor cells. One group, led by Carl June at theUniversity of Pennsylvania, began reporting eye-catching responsesto CAR therapy: patients with pounds of leukemia that melted away. At a meeting in New Orleans this month, June’s team and another at Memorial Sloan-Kettering Cancer Center in New York reported that the T cell therapy intheir studies put 45 of 75 adults and children with leukemia into complete remission, although some later relapsed. CAR therapy is now the focus of numerous clinical trials. Researchers hope that it, like the antibodies, can targetan assortment of cancers.

 

　Engineered T cellsare still experimental, but the antibodies areslowly going mainstream. At least five major drug companies, their early hesitancy gone, are developing antibodies such as anti–PD-1. In 2011, the U.S. Food and Drug Administration approved Bristol-Myers Squibb’s anti–CTLA-4 treatment,called ipilimumab, for metastaticmelanoma. The cost is high: The company charges $120,000 for a course of therapy. In 2012, Suzanne Topalian of Hopkins, Mario Sznol of Yale University, and their colleagues reported results foranti–PD-1 therapy in nearly 300 people, and they provided an update earlier this year. Tumors shrunk by about half ormore in 31% of those with melanoma, 29% with kidney cancer, and 17% with lung cancer.

 

　This year broughteven more encouragement. Bristol-Myers Squibb reported this fall that of 1800melanoma patients treated with ipilimumab, 22% were alive 3 years later. In June, researchers reported that combining ipilimumab and anti–PD-1 led to “deep and rapid tumor regression” in almost a third of melanoma patients. Drugs blocking the PD-1 pathway have not yet been proven to extend life, although survival rates so far have doctors optimistic that they do.

 

　For physiciansaccustomed to losing every patient with advanced disease, the numbers bring a hope they couldn’t have fathomed a few years ago. For those with metastatic cancer, the odds remain long. Today’s immunotherapies don’t help everyone, andresearchers are largely clueless as to why more don’t benefi t. They are racing to identify biomarkers that might offer answers and experimenting with ways to make therapies more potent. It’s likely that somecancers will not yield to immunotherapy for many years, if ever.

 

　Even in the fl uidstate oncology now fi nds itself, this much is certain: One book has closed, and a new one has opened. How it will end is anyone’s guess.

 

–JENNIFER COUZIN-FRANKEL

 

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