华盛顿大学医学院：疫苗可能使与癌症的战争个人化

Vaccines may make war on cancer personal

 

　

　

在不久的将来，医生可能会用刺激免疫系统攻击恶性肿瘤的个性化疫苗来治疗一些癌症患者。位于圣路易斯的华盛顿大学医学院的科学家们进行了一项新的研究，使这种方法离现实更近了一步。

 

就像流感疫苗一样，正在开发的癌症疫苗被设计用来提醒免疫系统警惕危险的入侵者。但是，疫苗不会为免疫系统攻击潜在的病原体攻击准备，而是帮助关键的免疫细胞识别已经存在于体内的癌细胞的独特特征。

 

在11月27日发表在《自然》(Nature)杂志上的新研究中，科学家们在计算机模拟、细胞培养和动物模型中测试了试验性疫苗。结果表明，这些疫苗可以使免疫系统破坏或缓解大量的肿瘤。例如，疫苗治愈了将近90%的患有晚期肌癌的老鼠。

 

“这强有力的证据表明，个性化癌症疫苗可以成为非常有效的癌症治疗方法，现在应该应用于人类癌症，”高级作者Robert Schreiber博士说。

　

 

华盛顿大学Siteman癌症中心和巴恩斯-犹太医院的科学家们正在使用这些疫苗来治疗多种癌症，包括乳腺癌、脑癌、肺癌和头颈癌。由Gerald Linette, MD, PhD，和Beatriz Carreno博士领导的这些研究中，最先进的是评估转移性黑色素瘤患者的个性化癌症疫苗。

 

这些疫苗正在与华盛顿大学(Washington University)基因组研究所(Genome Institute)的科学家合作开发。

 

创造一种个性化的疫苗是从病人的肿瘤和正常组织的DNA样本开始的。基因组研究所(Genome Institute)的研究人员对DNA进行排序，以识别突变的癌症基因，这些基因可以生成只有在肿瘤细胞中才有的蛋白质。然后他们分析这些蛋白质，以确定哪些最有可能被T细胞识别和攻击。这些蛋白质的一部分被整合到疫苗中给病人。

 

多年研究癌症遗传学和免疫系统与癌症的相互作用使疫苗策略成为可能。

 

这项技术的灵感来自一种叫做检查点封锁的疗法。这种基于免疫的癌症治疗方法在临床试验中已经成功地治疗了晚期肺癌和皮肤癌，它利用了许多肿瘤中存在的免疫T细胞，但这些T细胞被癌细胞阻断了。

 

癌细胞通过激活一种叫做检查点系统的安全机制来关闭T细胞。这个系统可以防止免疫细胞攻击人体自身的组织。

 

　

　

检查点封锁切断T细胞，释放它们对肿瘤的破坏性能力。但是这种方法也增加了同样的免疫细胞错误攻击健康组织的机会，导致严重的自身免疫性疾病。

 

Schreiber说:“我们认为找到识别突变肿瘤蛋白的方法会更安全，这些蛋白是重新激活的T细胞攻击肿瘤的具体目标。”“我们相信，我们可以将这些蛋白质结合到疫苗中，疫苗只能释放肿瘤上的T细胞，到目前为止，我们的试验非常成功。”

　

　

这项研究在一定程度上是由华盛顿大学人类免疫学和免疫治疗项目中心(Center for Human Immunology and immuntherapy program)促成的，该中心提供共享的实验室设施和其他支持，以帮助免疫治疗研究从基准到临床的发展。

 

这项研究得到了国家卫生研究院(NIH)、巴恩-犹太医院癌症前沿基金基金会、癌症研究所、苏珊·g·科门和WWWW基金会的资助。Gubin MM,张X,舒斯特尔H,卡隆E,病房JP,野口T,伊万诺娃Y,Hundal J,阿尔瑟CD,克雷布斯W-J,穆德通用电气,Toebes M,Vesely医学博士林构造论,科曼AJ,Allison JP,弗里曼GJ,夏普啊,皮尔斯EL,舒马赫TN,Aebersold R,Rammensee H g,Melief CJM,狂欢节,Gillanders我们Artyomov MN,施赖伯RD。

 

检查点封锁癌症免疫治疗肿瘤特异性抗原变异的目标。NATURE.2014年11月27日。

 

华盛顿大学医学院(Washington University School of Medicine)的2,100名教职员工和志愿医师也是巴恩-犹太人和圣路易斯儿童医院(St. Louis Children’s hospital)的医务人员。医学院是国内领先的医学研究、教学和护理机构之一，目前在美国新闻与世界报道中排名第六。通过与巴恩-犹太和圣路易斯儿童医院的合作，医学院与BJC HealthCare有关联。

 

Vaccines may make war on cancer personal

By Michael C. Purdy  November 26, 2014

 

In the near future, physicians may treat some cancer patients with personalized vaccines that spur their immune systems to attack malignant tumors. New research led by scientists at Washington University School of Medicine in St. Louis has brought the approach one step closer to reality.

 

Like flu vaccines, cancer vaccines in development are designed to alert the immune system to be on the lookout for dangerous invaders. But instead of preparing the immune system for potential pathogen attacks, the vaccines will help key immune cells recognize the unique features of cancer cells already present in the body.

 

 

In the new study, which appears Nov. 27 in an issue of Nature focused on cancer and the immune system, scientists tested investigational vaccines in computer simulations, cell cultures and animal models. The results showed that the vaccines could enable the immune system to destroy or drive into remission a significant number of tumors. For example, the vaccines cured nearly 90 percent of mice with an advanced form of muscle cancer.

 

“This is strong evidence that personalized cancer vaccines can be very effective cancer therapies and should be applied to human cancer now,” said senior author Robert Schreiber, PhD, the Alumni Professor of Pathology and Immunology and director of the university’s Center for Human Immunology and Immunotherapy Programs.

 

Scientists at the Siteman Cancer Center at Washington University and Barnes-Jewish Hospital are in the process of using these vaccines against many different types of cancers including breast, brain, lung, and head and neck cancers. The most advanced of these studies, led by Gerald Linette, MD, PhD, and Beatriz Carreno, PhD, is evaluating personalized cancer vaccines in patients with metastatic melanoma.

 

The vaccines are being developed in collaboration with scientists at The Genome Institute at Washington University.

 

Creating a personalized vaccine begins with samples of DNA from a patient’s tumor and normal tissue. Researchers at The Genome Institute sequence the DNA to identify mutant cancer genes that make versions of proteins found only in the tumor cells. Then they analyze those proteins to determine which are most likely to be recognized and attacked by T cells. Portions of these proteins are incorporated into a vaccine to be given to a patient.

 

Years of studying cancer genetics and of the immune system’s interactions with cancer have made the vaccine strategy possible.

 

The technique was inspired by a therapy scientists call checkpoint blockade. This immune-based cancer treatment, which has been successful against advanced lung and skin cancers in clinical trials, takes advantage of immune T cells that are present in many tumors but have been shut off by cancer cells.

 

The cancer cells shut off the T cells by activating a safety mechanism called the checkpoint system. This system helps prevent immune cells from attacking the body’s own tissues.

 

Checkpoint blockade takes the brakes off T cells, unleashing their destructive capabilities on the tumors. But the approach also increases the chances that those same immune cells erroneously will attack healthy tissue, causing serious autoimmune disease.

 

“We thought it would be safer to find ways to identify the mutated tumor proteins that are the specific targets of the reactivated T cells that attack the tumors,” Schreiber said. “We believe we can incorporate those proteins into vaccines that only unleash the T cells on the tumors, and so far, our tests have been very successful.”

 

The research was made possible in part by Washington University’s Center for Human Immunology and Immunotherapy Programs, which provides shared laboratory facilities and other support to aid the bench-to-bedside development of immunotherapy research.

 

This research was supported by grants from the National Institutes of Health (NIH), the Foundation for Barnes-Jewish Hospital Cancer Frontier Fund, the Cancer Research Institute, Susan G. Komen, and the WWWW Foundation.Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arther CD, Krebber W-J, Mulder GE, Toebes M, Vesely MD, Lam SSK, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee H-G, Melief CJM, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. Checkpoint blockade cancer immunotherapy targets tumor-specific mutant antigens. Nature. Nov. 27, 2014.

 

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

 

 

Vaccines may make war on cancer personal | The Source | Washington University in St. Louis  https://source.wustl.edu/2014/11/vaccines-may-make-war-on-cancer-personal/