斯坦博士里德尔，一个创新的肿瘤免疫治疗在弗雷德双雄，

StephenW

Dr. Stan Riddell, an Innovator in Cancer Immunotherapy at Fred Hutch, Presents at AAAS Annual Meeting
Released: 14-Feb-2016 4:05 PM EST
Source Newsroom: Fred Hutchinson Cancer Research Center   

Newswise — (SEATTLE – Feb. 14, 2016) – Dr. Stanley Riddell, an immunotherapy researcher and oncologist at Seattle’s Fred Hutchinson Cancer Research Center, presented on Feb. 14 an update on new adoptive T-cell strategies for cancer at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.

His presentation was part of a symposium on the promise and progress of T-cell therapy to fight human diseases. For more than 25 years, Riddell has pioneered experimental therapies that modify and empower the immune system to effectively treat cancers and infectious diseases.

In preliminary results of clinical trials using the latest version of an experimental immunotherapy – T cells engineered with chimeric antigen receptors, or CARs – Riddell and his colleagues have seen “sustained regression” in many previously relapsing and treatment-resistant cases of B-cell malignancies: acute lymphoblastic leukemia, Non-Hodgkin lymphoma and chronic lymphocytic leukemia. CARs are synthetic receptors that are delivered and linked to T cells by gene transfer techniques to redirect T-cell recognition to cancer cells. By introducing the CARs into specialized subsets of T cells, a potent and long-lasting immune response against the tumor can be achieved.

The studies are funded by Juno Therapeutics, which was initially formed on technology from researchers at Fred Hutch, Memorial Sloan-Kettering Cancer Center and Seattle Children’s Research Institute to commercialize promising immunotherapies.

“The merging of gene therapy, synthetic biology and cell biology is providing new treatment options for patients with refractory malignancies and represents a novel class of therapeutics with the potential to transform cancer care,” Riddell said. “In the laboratory and in clinical trials, we are seeing dramatic responses in patients with tumors that are resistant to conventional high-dose chemotherapy.”

T cells are white blood cells that detect foreign or abnormal cells, including cancerous ones, and initiate a process that targets the invaders for attack. But even when triggered, the natural immune response to a tumor often is neither potent nor persistent enough to vanquish cancer cells: T cells become exhausted or tumors evade them by imposing regulation that can limit the effectiveness of attack by T cells present in the patient.

Adoptive T-cell transfer is an experimental immune-boosting process in which immune cells are engineered to recognize and attack the patient’s cancer cells. Researchers extract T cells from the blood and use gene transfer to introduce highly potent receptors that target the cancer cell. In less than two weeks, the new cells are infused into the patient where they can home to the tumor site and destroy the cancer cells.

Riddell and his colleagues constantly refine the process. They recently revised their CAR T-cell treatment protocols to increase effectiveness and reduce negative side effects, which can include neurological symptoms and “cytokine release syndrome,” with fevers and drops in blood pressure. Meanwhile, scientists in his lab are working to modify the technology to apply it to a wider range of cancers, and they are developing the next generation of engineered T cells, which are expected to be safer and easier to design.

In his AAAS presentation, Riddell discussed these and other recent advances and outline steps researchers are taking to improve targeting and reduce side effects. His lecture, “Engineering T Cells for Safe and Effective Cancer Immunotherapy,” is one of three that will were presented.

Also at the symposium, Dr. Dirk Busch, an infection immunology researcher at the Technical University of Munich, Germany, discussed advanced cell-processing technologies that have been developed at the TUM and are being applied to gene and cell therapy, and a preclinical study aimed at safeguarding against treatment-related toxicity. Chiara Bonini, a research scientist in the Cancer Immunotherapy and Gene Therapy Program at San Raffaele Scientific Institute, Milan, Italy, provided a presentation on a T cell receptor gene-editing technique designed to improve therapeutic effectiveness while reducing toxicity risk.

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At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first and largest cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube

StephenW

斯坦博士里德尔，一个创新的肿瘤免疫治疗在弗雷德双雄，本集团于美国科学促进会年会
发行时间：14月 - 2016年4:05 PM EST
来源新闻：弗雷德·哈钦森癌症研究中心

新闻网 - （西雅图 - 2016年2月14日） - 斯坦利博士里德尔，免疫治疗研究员，肿瘤学家在西雅图的弗雷德·哈钦森癌症研究中心，提出了关于2月14日在股东大会上对癌症的新收养的T细胞策略更新美国科学发展协会在华盛顿特区的进步

他的介绍是在T细胞疗法的承诺和进步对抗人类疾病的专题讨论会的一部分。对于超过25年，里德尔率先实验性疗法修改和增强免疫系统，有效地治疗癌症和传染病。

在使用最新版本的实验免疫治疗临床试验的初步结果 - T细胞工程与嵌合抗原受体，汽车上 - 里德尔和他的同事在B细胞恶性肿瘤很多以前复发和难治性病例所看到的“持续回归” ：急性淋巴细胞白血病，非何杰金氏淋巴瘤和慢性淋巴细胞白血病。中亚是由基因转移技术递送和连接至T细胞的T细胞识别重定向到癌细胞合成受体。通过将汽车进入T细胞专门的子集，针对肿瘤一个有效的和持久的免疫反应就可以实现。

该研究是由朱诺治疗，这是初步形成技术研究人员弗雷德双雄，纪念斯隆 - 凯特琳癌症中心和西雅图儿童研究所看好的免疫疗法商业化的资助。

“基因疗法，合成生物学和细胞生物学的合并是难治恶性肿瘤提供新的治疗选择，代表一类新的具有变换癌症治疗的潜在治疗剂的，”里德尔说。 “在实验室和临床试验中，我们看到剧烈反应的患者的肿瘤是对传统的高剂量化疗抗性”。

T细胞是白血细胞，检测外来的或不正常的细胞，包括癌细胞的人，并启动靶向入侵者攻击的方法。但是触发即使当，至肿瘤的自然免疫反应常常是既有效的，也没有足够的持久性，以战胜癌细胞：T细胞耗尽或肿瘤通过施加调节可通过存在于病人的T细胞限制攻击的效力规避它们。

继T细胞转移是一个实验性免疫增强的过程中，免疫细胞被设计来识别和攻击患者的癌细胞。研究人员提取的血液和使用基因转移引入靶向癌细胞高度有效的受体的T细胞。在不到两周，新细胞注入患者，他们可以家庭对肿瘤部位和破坏癌细胞。

里德尔和他的同事不断完善的过程。他们最近修改了其CAR T细胞的治疗方案，以提高效率，减少负面影响，其中包括神经系统症状和“细胞因子释放综合征”有发烧和血压下降。同时，科学家们在他的实验室正在修改的技术，以将其应用到更广泛的癌症，以及他们正在开发下一代工程化的T细胞，这预计是更安全和更容易设计的。

在他的介绍AAAS，里德尔讨论这些和其他的最新进展和大纲步骤的研究人员正在改善目标，减少副作用。他的演讲，“工程性T细胞安全有效的癌症免疫疗法”，是将被提出了三个中的一个。

已经在慕尼黑工业大学已开发和正在应用基因和细胞治疗此外，在座谈会上，德克布希博士，德国慕尼黑技术大学的感染免疫学研究，讨论了先进的电池处理技术，以及临床前研究为了维护对治疗相关的毒性。基娅拉博尼尼，在癌症免疫治疗和基因治疗计划在圣拉斐尔科学研究所，意大利米兰的研究科学家，对旨在改善治疗效果，同时降低风险的毒性T细胞受体基因编辑技术提供了一个演示。

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在弗雷德·哈钦森癌症研究中心，拥有三个诺贝尔奖获得者，世界著名的科学家跨学科的团队寻求新的和创新的方法来预防，诊断和治疗癌症，艾滋病毒/艾滋病和其他危及生命的疾病。弗雷德双雄在骨髓移植的开创性工作导致免疫疗法的发展，它利用免疫系统的力量来治疗癌症用最小的副作用。一个独立的，非营利性研究机构总部设在西雅图的弗雷德双雄房子了全国第一个，也是最大的肿瘤防治研究项目，以及妇女健康倡议临床协调中心和艾滋病疫苗试验网络的国际总部。私人捐款是使弗雷德双雄科学家探索导致重大的医学突破新的研究机会至关重要。欲了解更多信息，请访问fredhutch.org或按照弗雷德双雄在Facebook，Twitter或YouTube的

StephenW

. CAR-T 2.0: Small studies spotlight promise of a breakthrough upgrade

Tuesday, February 16, 2016 | By John Carroll


TUM's Dirk Busch

About two years ago, adoptive T-cell therapies captured the attention of the R&D world with the initial round of dramatic results in fighting blood cancers. But even before that first wave of CAR-T drugs makes it to the market, some of the leading scientists in the field have been doing some extensive tinkering with the technology. And over the long weekend, several of the top CAR-T scientists in the world laid out fresh human and animal data indicating their progress in increasing the potency of the treatment while extending the durability of these drugs and potentially dialing down the threat of severe side effects.

This new work could play a particularly important role at Juno Therapeutics ($JUNO), the Seattle-based biotech that helped ignite tremendous excitement for the science with close ties to a range of leading cancer R&D institutions, which both acquired a key spinout less than a year ago and also funded the work on display over the weekend.

The autologous CAR-T approach that relies on patient cells is simple and broadly understood. After extracting T cells from patients, they're re-engineered with a chimeric antigen receptor so they can grapple with cancer cells. Juno, Kite Pharma ($KITE) and Novartis ($NVS) have all demonstrated in small studies just how effective an antigen-activated approach can be in fighting blood cancers, while staring down some tough obstacles in applying the same approach to solid tumors.

Dirk Busch from the Technical University of Munich, Chiara Bonini of the San Raffaele Scientific Institute in Milan, and Stanley Riddell of the Fred Hutchinson Cancer Research Center, though, managed to captivate an audience at the annual meeting of the American Association for the Advancement of Science with an update on their work.

They wanted to find a subset of T cells that offered the best prospects for a durable response that could last years with lower doses that could hopefully be used without the life-threatening instances of cytokine release syndrome that has limited the use of this approach.

These scientists captivated their audience with evidence that memory T cells are among the best candidates for the job.

"What we bring into the game is, first, the conviction that you have to select the right cells to generate optimal cell products for therapy, together with superior techniques to do it," noted TUM's Busch. "Over the past years, we at TUM as well as Stan Riddell and Chiara Bonini have worked on providing cell products that will upon transfer to patients expand to large numbers and stay active for a long time, potentially life-long. We identified a subset of T cells with high regenerative potential, where even low numbers of transferred cells--in the extreme a single T cell--can confer therapeutic immune responses."

In a small group of dying, late-stage patients given just months to live, this approach eliminated symptoms of acute lymphoblastic leukemia in 94% of the group. Patients with a variety of blood cancers saw an 80% response rate.

"This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients," Riddell told reporters at the meeting.

"This is really a revolution," Bonini added, according to The Guardian. "T cells are a living drug, and in particular they have the potential to persist in our body for our whole lives."

Juno has been paying close attention to these developments. Last May, the biotech acquired a spinout from TUM, Stage Cell Therapeutics, in a deal worth up to $233 million. And Juno also funded the work at the Hutch, which has been allied with the biotech from its launch date.

This won't be the last word on the subject, or anything close to it. Cellectis ($CLLS) has been pioneering an off-the-shelf approach to CAR-T that threatens to topple any autologous entry onto the market. Pfizer ($PFE) and Servier are now following up with their own human studies after the Paris-based biotech was able to use its technology successfully in a compassionate use case.

StephenW

CAR-T 2.0：小型研究的突破升级的焦点承诺

周二，2016年2月16日|由约翰·卡罗尔


慕尼黑工业大学的德克·布施

大约两年前，继T细胞疗法抓获研发世界的关注与打击血癌首轮戏剧性的结果。但CAR-T药物第一波使得市场之前，甚至，一些在该领域的顶尖科学家一直在做的一些技术广泛修修补补。而在长周末，几个世界顶级汽车-T的科学家奠定了表明自己的进步新鲜人类和动物的数据增加了治疗的功效，同时扩大这些药物的耐用性和潜在拨下来的严重副作用的威胁影响。

这种新的工作可以发挥在朱诺治疗（$ JUNO）特别重要的作用，总部位于西雅图的生物技术，帮助点燃有密切联系的科学的巨大兴奋了一系列领先的癌症研发机构，这既获得了关键的分拆小于一年前还资助周末展出的作品。

依赖于患者的细胞的自体CAR-T的方法是简单和广泛的理解。从患者提取T细胞后，他们与嵌合抗原受体重新设计，使他们能够与癌细胞斗争。朱诺，风筝制药（$ KITE）和诺华（$ NVS）都在小规模研究的抗原激活的方法可以只是如何有效打击血癌，而盯着在采用同样的方法，以实体瘤一些艰难的障碍证明。

德克 - 布希公司从慕尼黑技术大学，在米兰的圣拉斐尔科学研究所基娅拉博尼尼和弗雷德·哈钦森癌症研究中心的斯坦利·里德尔，虽然，管理在美国协会为的地位届年会吸引观众科学对他们的工作的最新情况。

他们想找到该供可能持续数年使用，可能希望不具有有限的使用这种方法的细胞因子释放综合征的危及生命的情况下，可以使用较低剂量的持久反应最好前景的T细胞的子集。

这些科学家迷住了观众的证据表明，记忆性T细胞是这个职位的最佳人选之一。

“我们把进入游戏是什么，首先，你必须选择合适的细胞产生治疗最佳细胞产品的信念，具有超强的技术一起做，指出：”TUM的布施。 “在过去的几年中，我们在慕尼黑工业大学以及斯坦里德尔和基娅拉博尼尼对提供电池产品，将在传递给患者扩大到大量，并保持活跃很长一段时间的工作，可能终生的。我们确定了一个子集的T细胞具有较高的再生潜能，甚至在那里转移细胞数量低 - 在极端的一个T细胞 - 可以赋予治疗的免疫反应。“

在一小群的死亡，只是给个月​​的生命晚期患者，这种方法可消除急性淋巴细胞白血病的症状群的94％。患者的各种血液癌症看到了一个80％的回应率。

“这是前所未有的药，说实话，让在此范围内的这些非常先进的患者应答率，”里德尔告诉记者，在本次会议。

“这的确是一场革命，”博尼尼补充说，根据监护人。 “T细胞是活的药物，特别是它们在我们的身体持续我们的整个生命的可能性。”

朱诺一直密切关注这些事态发展。去年5月，生物技术收购了TUM，舞台细胞治疗一个分拆，在一个交易价值高达2.33亿$。和朱诺还出资在​​双雄，已经联合了其上市日期的生物技术的工作。

这会不会是关于这个问题的最后一个字，或任何接近它。 Cellectis公司（$ CLLS）已开拓一个现成的现成做法，威胁推翻任何自体进入到市场CAR-T。辉瑞制药（PFE $）和施维雅公司正在跟进自己的人类研究总部设在巴黎生物技术能够在一个富有同情心的用例成功地使用它的技术后。

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