Viruses Are Recruited As Killer of Tumors
消滅腫瘤 徵召病毒上陣
By Rachel Nuwer

In the early 1900s, not much could be done for cancer patients. Unless surgeons could excise a tumor, the disease typically spelled a swift and inevitable end. But in dozens of published cases over the years, doctors noticed a peculiar trend: cancer patients sometimes enjoyed a brief reprieve from their malignancies when they caught a viral infection.
20世紀初，醫學界對癌症幾乎束手無策。除非醫師能夠切除腫瘤，否則病人通常必然不久於人世。然而在多年來公布的數十個病例中，醫界發現一種很特別的趨勢：癌症病人在受到病毒感染期間，病情有時候竟然短暫緩解。

It was not a coincidence. Common viruses sometimes attack tumor cells, researchers discovered. For decades, they tried to harness this phenomenon, to transform it into a cancer treatment. Now, after a long string of failures, they are nearing success with viruses engineered to kill cancer.
這不是巧合。研究人員發現，一般的病毒有時候會攻擊腫瘤細胞。他們窮數十年精力想要駕馭這種現象，用以治療癌症，歷經一連串失敗後，已接近以改造病毒消滅癌細胞的境界。

“It’s a very exciting time,” said Dr. Robert Martuza, chief neurosurgeon at the Massachusetts General Hospital. “I think it will work out in some tumor, with some virus.” Candidates are already in advanced trials, he noted.
麻省綜合醫院首席神經外科醫師馬度沙說：「這是令人振奮的一刻。我認為我們一定可以用某些病毒來消滅某些腫瘤。」他說，部分候選病毒已進入進階實驗階段。

Cancer cells are able to replicate wildly, but they cannot ward off infection as effectively as healthy cells. So scientists have been looking for ways to create viruses that are too weak to damage healthy cells yet strong enough to destroy tumor cells.
癌細胞能大量複製，卻無法像正常細胞般有效避免感染。因此科學家一直在設法培育毒性無法傷害正常細胞，但足以消滅腫瘤細胞的病毒。

Researchers began in 1904 when they discovered that women with cervical cancer temporarily recovered when given a rabies vaccination. By midcentury, physicians were administering live viruses to cancer patients.
醫界1904年發現罹子宮頸癌婦女接種狂犬病疫苗會短暫復元後展開研究，20世紀中葉醫師已開始為癌症病人施用活性病毒。

These experiments proved ill fated. The cancer returned, or – or the worst cases – the injections themselves caused “the development of lethal infection in the host,” according to a 1964 American Journal of Pathology report. The field was abandoned for a time.
實驗結果不佳。《美國病理學》期刊1964年刊載報告指出，癌症去而復返，注射甚至曾使病人「受到致命的感染」。醫界一度放棄了這方面的研究。

But in 1991, Dr. Martuza seized upon the idea of using the herpes simplex virus (HSV-1) as a cancer-fighter. The genome of HSV-1 is comparatively large and can accommodate a number of mutations and deletions. Dr. Martuza weakened the virus by removing some of its genes. The modified virus was injected into mice with brain cancer, and it did bring about remission. But most of the mice died of encephalitis.
1991年馬度沙想到以單純疹病毒（HSV-1）對付癌細胞。HSV-1基因組較大，能夠承受多種突變與刪減。馬度沙移除它的部分基因以降低毒性。他為患腦癌的老鼠注射經調整的病毒，病情果然緩解。然而多數老鼠最後死於腦炎。

In 1990, Bernard Roizman, a virologist at the University of Chicago, found a “master gene” in the herpes virus. When this gene is removed, the virus no longer has the strength to overcome healthy cells’ defenses. As it turned out, the modified virus was so crippled that it could only slow tumor growth.
1990年，芝加哥大學病毒學家羅伊斯曼在疹病毒當中發現「主宰基因」。病毒移除這個基因後再也無法擊潰正常細胞的防衛功能。事實證明，經修改的病毒毒性減弱到只能延緩腫瘤成長。

Then, in 1996, Dr. Ian Mohr, a virologist at New York University, happened on a way of further altering Dr. Roizman’s crippled virus. He exposed it repeatedly to cancer cells until a new viral mutant evolved with the ability to replicate in those cells. Dr. Mohr and a doctoral student, Matt Mulvey, then engineered a way for their virus to evade the immune system, making it an even more potent cancer-killing agent.
1996年，紐約大學病毒學家莫爾無意間找到進一步弱化羅斯曼病毒的方法。他不斷讓它接觸癌細胞，直到演化出能在這些細胞中複製的病毒突變體為止。接著，莫爾與博士生穆爾維設計出讓病毒避開免疫系統的方法，提高它殺滅癌細胞的能力。

Unlike in chemotherapy, which can diminish in effectiveness over time, oncolytic viruses multiply in the body and gain strength as the infection becomes established. In addition to attacking cancer cells directly, some also produce an immune response that targets tumors.
有別於效果遞減的化療，如果確定感染，溶瘤病毒會在體內增生，毒性也會增強。除直接攻擊癌細胞，部分病毒還會產生鎖定腫瘤的免疫反應。

Today, several potential cancer-fighting viruses are in trials, including two in Phase 3 trials.
目前有數種或可對抗癌細胞的病毒正在實驗中，其中二種已進入第三階段。

An engineered form of vaccinia – the viral agent that helped eradicate smallpox – is being tested against advanced liver cancer, the third leading cause of cancer deaths globally. In a recent trial, survival for patients treated with high doses of the virus, called JX-594, doubled to 14 months from 7, compared with that of patients treated with low doses.
牛痘是消滅天花的利器。科學家正在測試一種經過調整的牛痘，以治療高居全球癌症死因第三名的末期肝癌。在最近一項實驗中，以這種代號JX-594的高劑量病毒治療的病人與以低劑量治療者相比，存活期由七個月延長到14個月。

“To see that kind of response in a randomized trial is simply unheard of,” said Tony Reid, the director of clinical investigation at the Moores Cancer Center of the University of California, San Diego.
聖地牙哥加大摩爾斯癌症中心臨床研究主任雷德說：「隨機實驗有這種反應，聞所未聞。」

A herpes virus based on Dr. Mohr’s original discovery is in advanced trials against melanoma; initial data showed a 26 percent response rate in patient regression and survival.
以莫爾最初發現為基礎的一種疹病毒已進入對抗黑色素瘤的進階實驗階段。初步資料顯示病人復元、存活的反應比為26%。

A reovirus is being tested against head and neck cancers, often difficult to treat.
頭頸癌通常難以治療。醫界正在測試以一種呼吸道腸道病毒來治療。

According to the researchers, the side effects of treatment with these viruses are minimal, and include nausea, fatigue and aches.
研究人員指出，以這些病毒治療副作用很小，包括惡心、疲倦與疼痛。

Dr. Mulvey now heads a firm in Baltimore testing viruses to fight melanoma and bladder cancer. The biggest challenge now, he said, is simply convincing others that the new treatment is “not science fiction.”
穆爾維目前主持巴爾的摩一家公司，正在實驗以病毒對抗黑色素瘤與膀胱癌。他說，現階段最大挑戰是讓別人相信這種新療法「不是科幻小說的情節」。

“Thankfully, that hurdle is diminishing,” he said.
他說：「所幸這道障礙正在消失。」

原文參照：
http://www.nytimes.com/2012/03/20/health/research/viruses-are-recruited-and-flipped-as-cancer-killers.html

2012-04-03聯合報/G5版/UNITEDDAILYNEWS 陳世欽譯 原文參見紐時週報十版左