Vaccines may make war on cancer personal
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。
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。
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.
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