全球首宗！免疫療法「自救」治癒末期乳癌　網球般腫瘤消失了
撰文：李祖宏    2018-06-06 06:11    最後更新日期：2018-06-06 17:57

帕金斯（Judy Perkins）是美國佛羅里達州的一名工程師，在2003被確診患上乳腺癌，治療後平安度過了10年；可惜在2013年一次覆診中發現復發，先後接受了7種不同的化療及服用試驗性藥物都收效甚微，癌細胞更轉移至全身，肝臟長出網球般大的腫瘤，醫生當時認定她只剩3個月壽命，但世事往往難以逆料…..

帕金斯原先對免疫療法的效果也是半信半疑

帕金斯不時揹著背包攀山涉水。

在別無他法下，帕金斯在2015年12月參與了革命性的「過繼免疫療法」(Adoptive Cell Transfer)的臨床試驗，結果腫瘤被她自身免疫系統中的「T細胞」（T cells）清除，相關病變在一年內完全消失，帕金斯亦成為首名透過T細胞免疫療法治癒末期乳腺癌的病人；如今兩年多過去，她依然活得好好的。英國學術期刊《自然·醫學》（Nature Medicine）周一(4日)刊登了這宗病例。

「感覺到胸壁的腫瘤縮小了」

帕金斯有兩名分別18歲和20歲的兒子，她坦言得知癌細胞轉移時極度沮喪，「你不斷接受治療但卻不能治癒，每種治療的收效時間都較上一種為短，實在令人筋疲力盡。」當時她已辭去工作，安排身後事，並列出未了心願，包括要去一趟大峽谷。

帕金斯原先對免疫療法的效果也是半信半疑，「但在兩周內，我可以感覺到胸壁的腫瘤縮小了，開始覺得病情好轉，醫生們都對結果很滿意。」她記得在手術後的第一次掃描時，醫護人員都非常興奮和雀躍，並告訴她很有機會治癒。如今帕金斯已重過正常生活，揹背包攀山涉水，出海玩皮划艇都難不倒她，還剛剛花了5個星期時間去環遊佛羅里達州。

帕金斯現已重過正常生活，當然少不了戶外活動。

她說：「我猶如中了頭獎！那感覺很神奇，我身上已經兩年沒有發現癌細胞，專家們可能稱之為延長緩解期，但我稱之為治癒。」

900億細胞「奇兵」立大功

美國國家癌症研究所（National Cancer Institute）的研究人員當日首先是對帕金斯的腫瘤進行測序，在乳腺癌細胞中找到了62種不同的突變，並在腫瘤內分離出「腫瘤浸潤性T細胞」（Tumor-Infiltrating T Cells），此免疫細胞可識別患者體內的癌細胞並且主動攻擊；不過，分析的結果顯示，在62種突變中，那些T細胞僅識別到其中4種。由於T細胞的數量太少，作用有限，研究人員於是進行大量培養，再將為數約900億的T細胞輸回到帕金斯體內。

這種療法的原理是：人體免疫系統某部分一直努力對抗癌症，但更大部分因未能識別癌細胞而停止攻擊，T細胞可滲透腫瘤，只要有足夠數量就能對抗癌症。目前，僅15%接受如此「個人化」治療的癌症患者，獲得如帕金斯般的良好效果，研究團隊希望新療法可在5年內，適用於更多不同癌症患者身上。

文章來自: hk01

https://www.hk01.com/%E7%86%B1%E7%88%86%E8%A9%B1%E9%A1%8C/196023

________________________________________________________________________________________________

Judy Perkins during a 1,200-mile kayaking trip around the state of Florida.Courtesy Judy Perkins

It wasn’t looking good for Judy Perkins. Her breast cancer had come back with a vengeance after a 2003 mastectomy and she had big tumors in her chest and on her liver.

But an experimental new approach that combines new immunotherapy drugs with a tailor-made therapy to boost her own immune system pulled Perkins back from the brink of death. She’s just completed a 1,200-mile kayaking trip around the state of Florida and is looking forward to decades more of life.

“I hit the jackpot,” said Perkins, who is now 52 and cancer-free more than two years later.

Perkins really is lucky. The intensive, tailored approach only helps 15 percent of the patients who tried it, said Dr. Steven Rosenberg of the National Cancer Institute, who led the team that treated Perkins.

But Rosenberg, who has dedicated his career to finding a way to harness the body’s immune system to fight cancer, think her case has taken his quest a big step forward.

“We are getting better all the time,” said Rosenberg, whose findings are published in the journal Nature Medicine.

What his findings mean, he says, is that oncologists have to recognize that cancer is unique to every patient, and that treatments must reflect that.

“We have to develop a new drug for every patient,” Rosenberg said.

Perkins’ immune system was already trying to fight off the tumors that had spread across her torso. What Rosenberg aims to do is find and amplify the immune system cells that are doing the best job of it, even as they are overwhelmed by the cancer’s spread.

The team took samples of her tumors and sequenced their DNA. They also sampled tumor infiltrating lymphocytes, the immune system cells that were stuck to the outside of the tumors. After finding the genetic mutations that allowed the tumor cells to take over their victim’s body, Rosenberg’s team chose the immune cells that were latching onto those particular mutations most effectively.

“It’s a whole different way of thinking about cancer treatment.”

Those cells they grew outside Perkin’s body and then re-infused back into her system. They also dosed her with the immune-boosting drug interleukin 2, as well as with Keytruda, one of the newer immunotherapies that have been shown to have remarkable effects in certain cancers.

And she went through one last round of chemo to give the new lymphocytes room to take over.

It worked.

“The patient had these large, almost tennis-ball-sized lesions, one growing almost through her chest wall,” Rosenberg told NBC News.

“She had tumors throughout her belly and lymph nodes, and everything disappeared when we targeted four of the mutations that her tumors were expressing,” he added.

“She probably would have had two to three months to live had we not treated her.”

Before and after MRIs with TIL therapy

MRI scans of a woman with breast cancer before T-cell therapy show a lesion invading the chest wall, top left, and metastatic lesions in the liver, bottom left. Right: Scans 14 months after treatment show all lesions have disappeared.NCI

Perkins could feel one big tumor in her chest and she knew when the treatment started working. “That tumor I could palpate with my fingers and it started to get softer and shrink,” she said.

Targeted cancer drugs are formulated to match specific mutations seen in specific cancers. But Rosenberg said he has found that tumors in one patient have mutations that are different from those seen in other patients.

And while the new immunotherapy drugs help the body’s immune system recognize tumors, they only work in a small percentage of patients.

Rosenberg’s team often takes on last-ditch cases — people with months to live, whose cancer has come back again and again despite multiple treatments. He’s treated patients with liver cancer, bile duct cancer, melanoma and other cancers.

Only a few of them live, but those cases are spectacular.

Perkins knew this when she signed up for the trial.

“They told me they had treated 12 patients and were following up on one,” she said. “That means 11 died. I’m an engineer. I can do math. I know 11 out of 12 isn’t great odds.”

Perkins, who lives in Port Lucie, Florida, sent two friends with breast cancer to Rosenberg’s lab and both of them died despite the treatment — one of them with severe side-effects from the treatment itself, she said.

Rosenberg is quick to say the approach is not ready for commercial use, but he notes that CAR-T, a similarly personalized cancer treatment that works in blood cancers, that has been commercialized by companies including Kite Pharmaceuticals and Gilead Sciences.

CAR-T only works in blood cancers, Rosenberg said. A different tactic is needed for solid tumors, such as breast cancer. And even though it is very expensive and very complicated, CAR-T can be successful, he noted. “It’s a whole different way of thinking about cancer treatment,” he said.

“If you can develop treatments that can cure patients, people will want them.”

Cancer specialists not involved in the experiment called it a major advance. Dr. Laszlo Radvanyi of the Ontario Institute for Cancer Research in Toronto described it as “an unprecedented response in such advanced breast cancer”.

“We are now at the cusp of a major revolution,” Radvanyi wrote in a commentary.

“This particular technique is highly specialized and complex, meaning that it will not be suitable for many people, but it is exciting because it shows how the immune cells already inside cancers may be switched on and made to work better,” said Dr. Peter Johnson of Southampton General Hospital in Britain.

As for Perkins, she says she is no longer a “professional cancer patient”. “I got back to doing what I like to do,” she told NBC News.

The cancer forced her to drop plans to start nursing school after ending a career as an engineer. She had also started a “bucket list” of adventures and will continue ticking off experiences.

“We went rafting down the Grand Canyon,” said Perkins, who has two sons and two stepsons with her husband.

She just completed the Florida kayak trip and looks forward to more. “It’s 1,200 miles of pure suffering,” she said. “I loved every minute of it.”

文章來自: NBCnews

https://www.nbcnews.com/health/health-news/highly-personalized-treatment-saves-breast-cancer-patient-n879841