Finding a New Way To Attack Cancer Cells
找到攻擊癌細胞的新方法
By Claudia Dreifus

James P. Allison is the chairman of the immunology department at the University of Texas M.D. Anderson Cancer Center in Houston. His seminal research opened up a new field in cancer treatment: immunotherapy. Instead of poisoning a tumor or destroying it with radiation, Dr. Allison, 66, has pioneered ways to unleash the immune system to destroy a cancer. He has won the Louisa Gross Horwitz Prize, often a precursor to a Nobel. This interview with him has been edited.
詹姆斯．艾利森是休士頓德州大學安德森癌症中心免疫部門主任。他的開創性研究為癌症治療開啟了一個新領域：免疫療法。66歲的艾利森開創了啟動免疫系統來摧毀癌細胞的方法，而不是毒死一個腫瘤或是用放射線來把它摧毀。他獲得了霍維茨獎，這個獎經常是諾貝爾獎的前奏。以下這篇對他的專訪經過編輯。

Q. The class of drugs you’ve helped invent has been hailed as one of the first truly new cancer treatments in decades. What makes it so different?
問：你協助發明的這一類型藥物，被各界譽為幾十年來第一種真正的癌症新式療法之一。這類藥物為何如此不同？

A. In the 1980s, my laboratory did work on how the T-cells of the immune system, which are the attack cells, latch onto the cells infected with viruses and bacteria and ultimately kill them. That research led me to think that the immune system could be unleashed to kill cancers. Basically, I proposed that we should stop worrying about directly killing cancer cells and develop drugs to release those T-cells.
答：在1980年代，我的實驗室曾經做過一些研究，以了解免疫系統的攻擊細胞T細胞如何鎖定被病毒或細菌感染的細胞，最終殺死它們。那項研究引導我去思考，可否啟動免疫系統去殺死癌細胞。基本上，我建議我們應該停止再為如何直接殺死癌細胞而傷腦筋，轉而去研發能夠釋出這些T細胞的藥物。

Q. Looking to the immune system for a cancer therapy isn’t a new idea, is it?
問：從免疫系統找出治療癌症的方法，並非新構想，是嗎？

A. There was a surgeon named William Coley in the 19th century who’d noticed that cancer patients who’d gotten infections after surgeries tended to have fewer reoccurrences than those who hadn’t. He thought that there was something in bacteria that provoked the body to do something therapeutic, and he tried to develop treatments based on that.
答：19世紀有一位名叫威廉．柯雷的外科醫師，他發現在手術後有受到感染的癌症病人，癌症復發的情況比沒受感染的癌症病人少。他認為細菌中的某種東西啟動身體去做有療效的事，他試圖根據這一點研發治療方法。

Coley had some success. His ideas disappeared with the advent of radiotherapy, which became the acceptable treatment.
柯雷取得了一些成果。他的想法隨著放射線治療的問世而消失了，後者成為可為各界接受的治療方法。

Q. What did you discover?
問：你發現了什麼？

A. In the 1990s, my team and another group showed that there was a molecule on T-cells that actually acts like an off switch or a brake pedal when T-cells encounter an infected cell. Instead of attacking the cell, this molecule puts a kind of brake on the immune response. We call it a checkpoint. I wondered whether we could block this off switch to keep the T-cells turned on. And that’s what we did. We developed an antibody to plug this off-switch. It worked great in mouse models of many types of cancer.
答：在1990年代，我的團隊和另一團隊顯示，當T細胞碰到一個受感染細胞時，T細胞表面上有一個分子，實際上充當開關的關閉鈕或是煞車踏板。這個分子不去攻擊細胞，反而對免疫系統的反應踩煞車，我們稱之為免疫檢查點。我開始思索，我們是否能夠抑制這個關閉鈕的作用，讓T細胞維持開啟狀態。這就是我們做的。我們研發一種抗體去塞住這個開關的關閉鈕。這在許多種癌症的老鼠模型上非常有效。

More importantly, it worked for some people with skin cancer. The first drug developed out of this was Yervoy, which was approved by the American Food and Drug Administration in 2011 against metastatic and inoperable advanced melanomas.
更重要的是，它對部分的皮膚癌病患有效。基於此一理論研發出來的第一種藥物是「益伏」，美國食品藥物管理局2011年批准用來治療已轉移和無法手術切除的晚期黑色素瘤。

Long-term follow up of 5,000 melanoma patients who received it found that 22 percent survived for at least 10 years, some longer.
對5000名使用此藥的黑色素瘤病患的長期追蹤發現，22%的病患存活10年以上。

Q. Is that a good number?
問：這是理想的數字嗎？

A. These were patients with usually seven months, maybe a year, to live. A woman in Santa Monica was one of the first people to get the drug. She had two kids in high school. She’d failed at everything. And so Dr. Antoni Ribas at University of California, Los Angeles said: “Well, we’ve got this experimental thing. We don’t know if it will work. It may be toxic.” She said, “I’ll do anything if I can just live a few more months to see my son graduate high school.” And so they treated her. And her tumors went away within about four months. I met her 10 years later. She said, “You know, my kids are through school, married, starting families.”
答：這些病患通常只能活7個月，也許一年。聖塔莫尼卡的一名婦人是第一批使用這種藥的病患之一。她有兩個念高中的孩子。所有治療方法對她都無效。因此，洛杉磯加州大學的安東尼．李巴斯博士說：「這樣吧，我們拿到這種實驗藥。我們不知道是否有效，也許有毒。」她說：「只要我能再活幾個月，看到兒子從高中畢業，我願意做任何事。」因此，他們為她治療。她的腫瘤在大約四個月內消失了。我在10年後又見到了她。她說：「你知道嗎，我的孩子已念完書、結婚、成家了。」

Q. There’s a lot of cancer in your own family, isn’t there?
問：你本人的家族有很多人得癌症，不是嗎？

A. My mother died of lymphoma when I was 12. An uncle died of melanoma, another of lung cancer. Both my brothers had prostate cancer – one died from it. I was diagnosed with it, too. It was caught early. I had a prostatectomy. After seeing how fast it progressed on my brother and how gruesome it was, I said: “I’m not taking any chances. I’ll risk the side effects. Just get it out now.”
答：我12歲時，母親死於淋巴癌。我有一個叔叔（或舅舅）死於黑色素瘤，另一個死於肺癌。我的兩個兄弟都罹患攝護腺癌，一個死於這種癌。我也診斷出罹患這種癌，發現得早。我做了攝護腺切除手術。看到我兄弟的癌症惡化得多麼快，多麼可怕之後，我說：「我不要冒險，我寧可冒有副作用的風險。現在就把它除掉。」

Q. Does it give you satisfaction that you’ve dealt a blow to something that’s caused your family such devastation?
問：你痛擊了讓你家族如此悲慘的東西，是否給你滿足感？

A. I’ve thought about it, and I think my mother and brother would be proud. Since Yervoy, there’ve been two other drugs of this type to win F.D.A. approval. And there have been trials with other cancers using Yervoy. It hasn’t been approved yet, but there have been responses with clinical benefits for prostate, kidney and bladder cancers. At this moment, just about every pharmaceutical company working the cancer space is working on immunotherapy drugs.
答：我想過這件事，我認為我母親和兄弟會為我感到驕傲。在「益伏」之後，有另外兩種這類型的藥物獲得食品藥物管理局通過。也有用「益伏」治療其他癌症的實驗，尚未獲得批准，不過臨床實驗的反應對攝護腺癌、腎臟癌和膀胱癌有益處。現在，幾乎所有研究癌症方面的製藥公司，都在研究免疫療法藥物。

原文參照：
http://www.nytimes.com/2015/03/03/science/arming-the-immune-system-against-cancer.html

2015-03-17聯合報/G5版/UNITED DAILY NEWS 田思怡譯 原文參見紐時週報十版左