Billions of T-cells clear woman’s breast cancer in study 數十億T細胞 在研究中徹底清除乳癌

Sun, Jun 10, 2018 - Page 9

An experimental therapy that extracts and multiplies powerful immune-system cells from inside tumors eradicated a patient’s breast cancer, a scientific first that could lead to new ways of treating malignancies that have resisted all other efforts.

Researchers at the US National Cancer Institute gave the experimental treatment to a 49-year-old woman whose cancer came roaring back after a decade in remission. The woman had tennis-ball-sized tumors in her liver and growing through her chest wall. Despite seven types of chemotherapy and hormonal therapy, her disease was still growing.

Using a biopsy, researchers plucked rare cells custom-made by the immune system from inside tumors, but in numbers too small to help a patient on their own. They grew copies of the cells in the lab, multiplying them into billions over a period of weeks. They were then infused back into the patient.

Two-and-a-half years after getting the new cells, the woman is cancer-free. The method, while still in its infancy, also shrank hard-to-treat tumors in six other patients with colon and cervical cancers, said Steven Rosenberg, chief of surgery at the institute.

“They are attacking their own cancers,” Rosenberg said in an interview. “It’s as highly personalized as a treatment can be. We are creating a new drug for every patient, targeting the unique mutations in that same patient’s cancer.” So far, the researchers have treated 40 patients, all with types of tumors that account for 80 percent of cancer deaths, according to Rosenberg. Seven have responded to the therapy.

The immunotherapy field has seen major breakthroughs in the past year, including the approval of two so-called CAR-T (chimeric antigen receptor T-cells) treatments from Gilead Sciences Inc and Novartis AG that extract T-cells from a patient’s blood and re-engineer them to recognize malignancies. Drugmakers have had less success using that technique on widespread solid tumors.

Rosenberg’s team takes a different tack. The researchers isolate rare T-cells that each patient produces in response to unique mutations that fuel the development of their cancer. Minute amounts of these natural T-cells infiltrate the tumor, though they aren’t present in high enough quantities to combat the growing cancer, Rosenberg said. After extracting the tumor-infiltrating lymphocytes from a biopsy, his team can multiply the cells and give billions of them back to the patient.

The group is getting better at identifying the rare T-cells that can attack the tumor, finding three times more of them in samples than they were even three months ago, Rosenberg said. There is still a long way to go, he said, but it’s an approach that isn’t specific to a certain cancer type, meaning it could evolve into an effective therapy for many forms of the disease, he said.

The results were published Monday in the scientific journal Nature Medicine.

(Bloomberg)

日前,一項實驗性療法從腫瘤中萃取並增殖強力的免疫系統細胞,成功的徹底清除一名病人的乳癌。這項科學首例有望帶來新治療方法,對付頑強抵抗其他治療方式的惡性腫瘤。

美國國家癌症研究所的研究人員,對一位四十九歲的女性施予此項實驗性療法。這位女性經過十年的緩解期後,癌症再度復發。她在肝臟和胸廓中長出的腫瘤約有網球般大小。儘管歷經七種不同化療和(抗)荷爾蒙治療法,病情仍然持續加劇。

藉由活體組織切片,研究人員從腫瘤摘取出免疫系統特別為腫瘤量身打造的稀有細胞。這些細胞數量太少,並不足以幫助病人。研究人員遂讓這些細胞在實驗室中增殖,使它們數量在幾個星期後達到數十億之譜,再將它們注入病人體內。

獲得新細胞的兩年半後,該女性的癌症完全消失。該研究所外科主任史蒂芬‧羅森伯格表示,雖然這個療法仍然處於發展初期,卻也縮小了另外六位罹患結腸癌與子宮頸癌病人身上頑強的腫瘤。

「這些病人正在攻擊他們自己的腫瘤,」羅森伯格在訪談中說明。「這可說是最高度個人化的治療方法。我們正在為每一位病人研發新藥物,標靶目標就是病人身上獨特的癌症突變。」到目前為止,研究人員對四十名病人進行治療,他們的腫瘤類型佔癌症死亡人數的百分之八十。其中,七名病人對此療法產生良好反應。

過去一年來,免疫療法領域出現重大的突破性進展,包括吉利德科學公司與諾華製藥這兩間公司的CAR-T(嵌合抗原受體T細胞)療法獲得核准。該療法從病人的血液中萃取出T細胞,並利用基因工程技術重新改造,讓這些細胞能夠辨識惡性腫瘤。不過,藥廠對擴散的實質固態瘤上使用這項技術時,並未獲得太大的成功。

羅森伯格的團隊採取另一個切入方向。由於每一位病人身上加速癌症發展的突變現象都是獨一無二的,研究人員遂將病人身體為對抗突變而製造的稀有T細胞分離出來。羅森伯格指出,微少的天然T細胞平常就滲透於腫瘤中,只是它們存在的數量並不足以打擊持續成長的癌症。從活體組織切片萃取出滲透腫瘤的淋巴球後,該研究團隊就能使它們增殖,再將數十億個淋巴球送回病人體內。

羅森伯格表示,研究團隊愈來愈善於辨識能攻擊腫瘤的T細胞,現在從樣本中找出的數量比起三個月前成長了三倍。他也說,雖然還有很長的一段路要走,但這並不是針對特定癌症種類的治療方式,也就是說,這個途徑能逐步發展成為對付不同型態癌症的有效治療方式。

這份研究結果週一發表於科學期刊《自然醫學》。

(台北時報章厚明譯)