卵巢癌:随着新的T细胞研究，有效的免疫治疗逐渐接近

Ovarian cancer: Effective immunotherapy steps closer with new T cell study

　

　

来源：

Ovarian cancer: Effective immunotherapy steps closer with new T cell study  https://www.medicalnewstoday.com/articles/316763.php?sr

由Catharine Paddock博士于2017年4月5日星期三出版

 

在本周的一次科学会议上，研究人员报告了卵巢癌免疫疗法的一些进展。然而，他们也概述了在治疗对这种和其他有实体肿瘤的癌症有效之前仍然存在的相当大的挑战。

 

T细胞攻击癌细胞

这项新的研究报告了一些成功的改造免疫系统T细胞攻击卵巢癌细胞，但研究人员警告说，在免疫疗法为卵巢癌患者的临床试验做好准备之前，仍有一些重大挑战需要克服。

 

来自西雅图弗雷德·哈钦森癌症研究中心(弗雷德·哈奇)的研究人员在华盛顿特区的美国癌症研究协会的年度会议上公布了这一发现。

 

美国癌症协会(American Cancer Society)的估计显示，在美国，大约22,440名女性将被诊断为卵巢癌，2017年将有约14,000人死于卵巢癌。

 

癌症始于卵巢的细胞——仅在女性体内发现的生殖腺。每个女性通常有两个卵巢，位于骨盆内子宫的两侧。卵巢产生的卵子通过输卵管进入子宫。如果卵子被男性精子受精，它就会发育成胎儿。

 

弗雷德·哈奇(Fred Hutch)的免疫疗法研究员克里斯汀·安德森(Kristin Anderson)博士在会议上介绍了这一发现。他说，尽管卵巢癌在美国并不像其他实体肿瘤癌症那样常见，但它的生存率很低，复发率也很高。主要原因是肿瘤并不会引起明显的症状，而且在被诊断出来的时候往往会恶化。

 

免疫疗法是一种相对较新的医学领域，在癌症治疗中显示出很有希望的结果。这种方法利用病人自身的免疫系统来对抗疾病。

　

　

 

实体肿瘤的T细胞移植经验

这项新研究涉及一种叫做过继T细胞转移(Adotive T-cell Transfer)的方法。在这种方法中，一种叫做T细胞的免疫细胞从病人的血液中提取出来，经过训练，可以瞄准并摧毁癌细胞。然后，在实验室中繁殖后，被活化的细胞被送回病人的体内。有时会使用供体细胞。

　

　

 

关于卵巢癌的快速事实

在美国美国女性一生中患卵巢癌的风险约为每75个女性中有一个会患上卵巢癌。

大约有一半的确诊病例发生在63岁以上的女性身上。

在过去的20年里，诊断率一直在缓慢下降。

 

了解更多关于卵巢癌的信息

Fred Hutch有很多研究免疫治疗癌症治疗的团队。安德森博士和他的同事报告说，采用T细胞移植治疗血癌是成功的。

 

在她的会议报告中，安德森博士报告了将从这项工作中学到的经验应用于实体肿瘤治疗的进展。

研究人员发现，卵巢癌细胞会过度产生两种蛋白质——WT1和mesothelin——并在实验室中证明，针对它们的T细胞可以杀死小鼠和人类卵巢癌细胞。

 

他们还发现，在卵巢癌的小鼠模型中，改造T细胞显著提高了存活率。

　

 

然而，安德森博士警告说，在采用T细胞移植技术用于人类患者的临床试验之前，仍有一段路要走。

 

研究小组发现，与治疗血癌相比，将T细胞疗法应用于乳腺癌、卵巢癌、肺癌和胰腺癌等实体肿瘤要困难得多。

 

在白血病和淋巴瘤中，改造T细胞可以直接注入到血液中以治疗血癌。然而，接触隐藏在体内的实体肿瘤会带来一些重大挑战。这些都是关于肿瘤微环境（TUMOR MICROENVIRONMENT）的问题——肿瘤内和周围的非癌细胞、分子和细胞外基质的混合物。

 

肿瘤微环境的挑战需要克服

安德森博士概述了他们正在研究的肿瘤微环境所带来的三个特殊挑战。一个是肿瘤微环境中有细胞和蛋白质向T细胞发送信号告诉它们关闭或忽略肿瘤细胞。

 

研究小组认为，目前有一些叫做检查点抑制剂的药物可以用来解决这个问题。另一种方法是设计T细胞来阻止这些特殊的信号。

 

第二个挑战是卵巢肿瘤细胞和邻近的血管向T细胞发送自毁信号，导致它们在攻击癌细胞之前自杀。

 

弗雷德·哈奇团队已经在研究第二种挑战的解决方案，即融合蛋白，当T细胞接收到这些自毁信号时，融合蛋白可以增强其抗癌活性。

 

研究人员在实体肿瘤微环境中发现的第三个挑战是低糖问题。为了像它们一样快速生长，卵巢癌细胞会吞噬它们从环境中获得的糖分。

 

然而，经过基因改造的T细胞也需要这种糖来刺激他们的旅程，并攻击癌细胞。弗雷德·哈奇(Fred Hutch)的研究人员正在寻找一种方法来设计T细胞，以便它们使用不同的能量来源。

 

安德森博士说，虽然他们目前关注的是卵巢癌，但他们相信，这些解决方案也将有助于在将领养T细胞转移到其他实体肿瘤上取得进展。

 

“如果我们能解决一些真正困扰我们的难题，那么我们就能更容易地将(解决方案)应用到那些障碍较少的癌症上，”她解释道，总结道:

　

“肿瘤微环境问题与实体肿瘤密切相关。”

 

该研究小组希望在未来几年内开展一项针对卵巢癌采用T细胞转移的人体临床试验。

 

 

 

Ovarian cancer: Effective immunotherapy steps closer with new T cell study

Published      Wednesday 5 April 2017 By Catharine Paddock PhD     

At a scientific meeting this week, researchers report some progress in developing an immunotherapy for ovarian cancer. However, they also outline the considerable challenges that remain before the treatment can be made effective for this and other cancers that have solid tumors.

T cells attack cancer cell

The new research reports some success in engineering immune system T cells to attack ovarian cancer cells, but the researchers caution that there are still some major challenges to overcome before the immunotherapy is ready for clinical trials in patients with ovarian cancer.

The researchers - from the Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle, WA - presented the findings at the annual meeting of the American Association of Cancer Research in Washington, D.C.

 

Estimates from the American Cancer Society suggest that, in the United States, around 22,440 women will be diagnosed with ovarian cancer and approximately 14,000 will die from the disease during 2017.

 

The cancer begins in cells of the ovaries - reproductive glands found only in women. Each woman normally has two ovaries, situated on each side of the uterus inside the pelvis. The ovaries produce eggs that travel to the uterus through the fallopian tubes. If an egg is fertilized by male sperm, it develops into a fetus.

 

Dr. Kristin Anderson, an immunotherapy researcher at Fred Hutch who presented the findings at the meeting, says that while ovarian cancer is not as common in the U.S. as other cancers with solid tumors, it has a low rate of survival and a high rate of relapse. The main reason is that the cancer does not cause obvious symptoms and is often advanced by the time it is diagnosed.

 

Immunotherapy is a relatively new area of medicine that is showing promising results in the treatment of cancer. The approach uses the patient's own immune system to fight disease.

 

 

Adoptive T cell transfer lessons for solid tumors

The new study concerns a method called adoptive T cell transfer. In this approach, immune cells called T cells are taken from the patient's own blood and trained to target and destroy cancer cells. Then, after multiplying in the laboratory, the primed cells are returned to the patient's body. Sometimes donor cells are used instead.

 

Fast facts about ovarian cancer

In the U.S., a woman's risk of developing ovarian cancer in her lifetime is around 1 in 75.

Around half of diagnosed cases are in women aged 63 and older.

Rates of diagnosis have been falling slowly over the past 20 years.

Learn more about ovarian cancer

Fred Hutch have a number of teams researching immunotherapy cancer treatments. In particular, Dr. Anderson and colleagues have reported success in using adoptive T cell transfer to treat blood cancers.

 

In her meeting presentation, Dr. Anderson reported progress on applying lessons learned from that work to the treatment of solid tumors.

 

The researchers found that ovarian cancer cells overproduce two proteins - WT1 and mesothelin - and showed that T cells engineered to target them can kill mouse and human ovarian cancer cells in the laboratory.

 

They also found that the engineered T cells significantly increased survival in a mouse model of ovarian cancer.

 

However, Dr. Anderson cautions that there is still some way to go before adoptive T cell transfer is ready for clinical trials in human patients.

 

The team discovered that, compared with treating blood cancers, it is much harder to apply T cell therapy to solid tumors like breast, ovarian, lung, and pancreatic cancers.

 

In leukemia and lymphoma, the engineered T cells can be infused directly into the bloodstream to target the blood cancer. However, access to solid tumors that are tucked away inside the body poses some major challenges. Among these are issues concerning the tumor microenvironment - a mixture of noncancerous cells, molecules, and extracellular matrix in and around the tumor.

 

 

Tumor microenvironment challenges to overcome

Dr. Anderson outlines three particular challenges posed by the tumor microenvironment that they are working on. One is the fact that there are cells and proteins in the tumor microenvironment that send signals to the T cells that tell them to shut down or simply ignore the tumor cells.

 

The team suggests that there are some existing drugs called checkpoint inhibitors that they could explore to tackle this problem. Another approach could be to engineer the T cells to block these particular signals.

 

The second challenge is that ovarian tumor cells and neighboring blood vessels send self-destruct signals to the T cells, causing them to commit suicide before they can attack cancer cells.

 

The Fred Hutch team is already working on a solution to this second challenge in the form of a fusion protein that boosts the T cells' anticancer activity when they receive these self-destruct signals.

 

The third challenge that the researchers have identified in the solid tumor microenvironment is the problem of low sugar. To grow as rapidly as they do, ovarian cancer cells devour sugar, which they get from their environment.

 

 

However, the engineered T cells also need this sugar to fuel their journey to, and attack on, the cancer cells. The researchers at Fred Hutch are looking for a way to engineer the T cells so that they use a different source of energy.

 

Dr. Anderson says that while they are currently focusing on ovarian cancer, they believe that these solutions will also help to make progress on using adoptive T cell transfer with other solid tumors.

 

"If we can solve some of the issues that really plague us with these hard ones, then we can more readily apply [the solutions] to cancers that have fewer of these hurdles," she explains, as she concludes:

 

"Tumor microenvironment issues come hand-in-hand with working on solid tumors."

The team hopes to start a human clinical trial of adoptive T cell transfer for ovarian cancer in the next few years.

Ovarian cancer: Effective immunotherapy steps closer with new T cell study  https://www.medicalnewstoday.com/articles/316763.php?sr