|By PR Newswire||
|December 9, 2012 06:01 PM EST||
University of Pennsylvania Researchers Report on Results of Trial in 12 Patients, Including Two Children
ATLANTA, Dec. 9, 2012 /PRNewswire-USNewswire/ -- Nine of twelve leukemia patients who received infusions of their own T cells after the cells had been genetically engineered to attack the patients' tumors responded to the therapy, which was pioneered by scientists in the Perelman School of Medicine at the University of Pennsylvania. Penn Medicine researchers will present the latest results of the trial today at the American Society of Hematology's Annual Meeting and Exposition.
The clinical trial participants, all of whom had advanced cancers, included 10 adult patients with chronic lymphocytic leukemia treated at the Hospital of the University of Pennsylvania (HUP) and two children with acute lymphoblastic leukemia treated at the Children's Hospital of Philadelphia. Two of the first three patients treated with the protocol at HUP – whose cases were detailed in the New England Journal of Medicine and Science Translational Medicine in August 2011 – remain healthy and in full remissions more than two years after their treatment, with the engineered cells still circulating in their bodies. The findings reveal the first successful and sustained demonstration of the use of gene transfer therapy to turn the body's own immune cells into weapons aimed at cancerous tumors.
"Our results show that chimeric antigen receptor modified T cells have great promise to improve the treatment of leukemia and lymphoma," says the trial's leader, Carl June, M.D., the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center. "It is possible that in the future, this approach may reduce or replace the need for bone marrow transplantation."
The results pave the way for a potential paradigm shift in the treatment of these types of blood cancers, which in advanced stages have the possibility of a cure only with bone marrow transplants. That procedure requires a lengthy hospitalization and carries at least a 20 percent mortality risk -- and even then offers only a limited chance of cure for patients whose disease has not responded to other treatments.
Three abstracts about the new research will be presented during the ASH meeting. David Porter, M.D., director of Blood and Marrow Transplantation in the Abramson Cancer Center, will give an oral presentation of Abstract #717 on Monday, Dec. 10, at 5 P.M. in the Thomas Murphy Ballroom 4, Level 5, Building B of the Georgia World Congress Center. Michael Kalos, Ph.D., director of the Translational and Correlative Studies Laboratory at Penn, will give an oral presentation on Abstract #756 on Monday, Dec. 10, at 5:45 P.M. in C208-C210, Level 2, Building C. Stephan Grupp, M.D., Ph.D., director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, will present a poster of Abstract #2604 on Sunday, Dec. 9, at 6 P.M. in Hall B1-B2, Level 1, Building B.
The protocol for the new treatment involves removing patients' cells through an apheresis process similar to blood donation, and modifying them in Penn's cell and vaccine production facility. Scientists there reprogram the patients' T cells to target tumor cells through a gene modification technique using a HIV-derived lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19.
The modified cells are then infused back into the patient's body following lymphodepleting chemotherapy. Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL and ALL tumor cells, and normal B cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T cells, which limits systemic side effects typically experienced during traditional therapies.
In addition to initiating the death of the cancer cells, a signaling molecule built into the CAR also spurs the cell to produce cytokines that trigger other T cells to multiply -- building a bigger and bigger army until all the target cells in the tumor are destroyed.
In the patients who experienced complete remissions after treatment, the CAR T cells exhibited vigorous proliferation after infusion, with the most robust expansion activity usually occurring between 10 and 31 days after infusion. Each of these patients developed a cytokine release syndrome -- marked by fever, nausea, hypoxia and low blood pressure -- which doctors treated when needed with the anti-cytokine agent tocilizumab. Ultimately, the modified T cell treatment eradicated large amounts of tumor in these patients.
Tests of patients with complete responses also show that normal B cells have been eliminated along with their tumors. Since these cells are important for the body's immune system to fight infection, the patients now are receiving regular gamma globulin treatments as a preventive measure. No unusual infections have been observed.
In August 2012, the University of Pennsylvania and Novartis announced an exclusive global research and licensing agreement to further study and commercialize these novel cellular immunotherapies using chimeric antigen receptor (CAR) technologies. As part of the transaction, Novartis acquired exclusive rights from Penn to CART-19, the therapy that was the subject of this clinical trial and which is now known as CTL019. Together, Penn and Novartis will build a first-of-its-kind Center for Advanced Cellular Therapies (CACT) in Philadelphia, which will be devoted to the discovery, development and manufacturing of adoptive T cell immunotherapies through a joint research and development program led by scientists and clinicians from Penn and Novartis.
The research was supported by the Leukemia & Lymphoma Society (June is the leader of one of the LLS's $6.25 million Specialized Center of Research grants), the Alliance for Cancer Gene Therapy, and the National Institutes of Health (1R01CA165206 and R01 CA138738).
Patients seeking information about this trial may visit http://www.penncancer.org/Tcelltherapy/.
Editor's notes: The University of Pennsylvania has licensed this technology to Novartis. Some of the scientists involved in these trials are inventors of this technology.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
SOURCE Perelman School of Medicine at the University of Pennsylvania
Even though you are running an agile development process, that doesn’t necessarily mean that your performance testing is being conducted in a truly agile way. Saving performance testing for a “final sprint” before release still treats it like a waterfall development step, with all the cost and risk that comes with that. In this post, we will show you how to make load testing happen early and often by putting SLAs on the agile task board.
Sep. 5, 2015 09:00 AM EDT Reads: 124
Manufacturing connected IoT versions of traditional products requires more than multiple deep technology skills. It also requires a shift in mindset, to realize that connected, sensor-enabled “things” act more like services than what we usually think of as products. In his session at @ThingsExpo, David Friedman, CEO and co-founder of Ayla Networks, will discuss how when sensors start generating detailed real-world data about products and how they’re being used, smart manufacturers can use the ...
Sep. 5, 2015 09:00 AM EDT Reads: 128
The 5th International DevOps Summit, co-located with 17th International Cloud Expo – being held November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA – announces that its Call for Papers is open. Born out of proven success in agile development, cloud computing, and process automation, DevOps is a macro trend you cannot afford to miss. From showcase success stories from early adopters and web-scale businesses, DevOps is expanding to organizations of all sizes, including the ...
Sep. 5, 2015 09:00 AM EDT Reads: 1,680
The Internet of Things is in the early stages of mainstream deployment but it promises to unlock value and rapidly transform how organizations manage, operationalize, and monetize their assets. IoT is a complex structure of hardware, sensors, applications, analytics and devices that need to be able to communicate geographically and across all functions. Once the data is collected from numerous endpoints, the challenge then becomes converting it into actionable insight.
Sep. 5, 2015 09:00 AM EDT Reads: 157
Moving an existing on-premise infrastructure into the cloud can be a complex and daunting proposition. It is critical to understand the benefits as well as the challenges associated with either a full or hybrid approach. In his session at 17th Cloud Expo, Richard Weiss, Principal Consultant at Pythian, will present a roadmap that can be leveraged by any organization to plan, analyze, evaluate and execute on a cloud migration solution. He will review the five major cloud transformation phases a...
Sep. 5, 2015 08:45 AM EDT Reads: 147
While many app developers are comfortable building apps for the smartphone, there is a whole new world out there. In his session at @ThingsExpo, Narayan Sainaney, Co-founder and CTO of Mojio, will discuss how the business case for connected car apps is growing and, with open platform companies having already done the heavy lifting, there really is no barrier to entry.
Sep. 5, 2015 08:45 AM EDT Reads: 240
As more intelligent IoT applications shift into gear, they’re merging into the ever-increasing traffic flow of the Internet. It won’t be long before we experience bottlenecks, as IoT traffic peaks during rush hours. Organizations that are unprepared will find themselves by the side of the road unable to cross back into the fast lane. As billions of new devices begin to communicate and exchange data – will your infrastructure be scalable enough to handle this new interconnected world?
Sep. 5, 2015 08:30 AM EDT Reads: 294
DevOps Summit, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long development...
Sep. 5, 2015 08:30 AM EDT Reads: 1,675
Through WebRTC, audio and video communications are being embedded more easily than ever into applications, helping carriers, enterprises and independent software vendors deliver greater functionality to their end users. With today’s business world increasingly focused on outcomes, users’ growing calls for ease of use, and businesses craving smarter, tighter integration, what’s the next step in delivering a richer, more immersive experience? That richer, more fully integrated experience comes ab...
Sep. 5, 2015 08:00 AM EDT Reads: 769
Consumer IoT applications provide data about the user that just doesn’t exist in traditional PC or mobile web applications. This rich data, or “context,” enables the highly personalized consumer experiences that characterize many consumer IoT apps. This same data is also providing brands with unprecedented insight into how their connected products are being used, while, at the same time, powering highly targeted engagement and marketing opportunities. In his session at @ThingsExpo, Nathan Trel...
Sep. 5, 2015 08:00 AM EDT Reads: 318
Puppet Labs is pleased to share the findings from our 2015 State of DevOps Survey. We have deepened our understanding of how DevOps enables IT performance and organizational performance, based on responses from more than 20,000 technical professionals we’ve surveyed over the past four years. The 2015 State of DevOps Report reveals high-performing IT organizations deploy 30x more frequently with 200x shorter lead times. They have 60x fewer failures and recover 168x faster
Sep. 5, 2015 08:00 AM EDT Reads: 165
The 3rd International WebRTC Summit, to be held Nov. 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA, announces that its Call for Papers is now open. Topics include all aspects of improving IT delivery by eliminating waste through automated business models leveraging cloud technologies. WebRTC Summit is co-located with 15th International Cloud Expo, 6th International Big Data Expo, 3rd International DevOps Summit and 2nd Internet of @ThingsExpo. WebRTC (Web-based Real-Time Com...
Sep. 5, 2015 07:15 AM EDT Reads: 1,653
Contrary to mainstream media attention, the multiple possibilities of how consumer IoT will transform our everyday lives aren’t the only angle of this headline-gaining trend. There’s a huge opportunity for “industrial IoT” and “Smart Cities” to impact the world in the same capacity – especially during critical situations. For example, a community water dam that needs to release water can leverage embedded critical communications logic to alert the appropriate individuals, on the right device, as...
Sep. 5, 2015 07:15 AM EDT Reads: 186
SYS-CON Events announced today the Containers & Microservices Bootcamp, being held November 3-4, 2015, in conjunction with 17th Cloud Expo, @ThingsExpo, and @DevOpsSummit at the Santa Clara Convention Center in Santa Clara, CA. This is your chance to get started with the latest technology in the industry. Combined with real-world scenarios and use cases, the Containers and Microservices Bootcamp, led by Janakiram MSV, a Microsoft Regional Director, will include presentations as well as hands-on...
Sep. 5, 2015 07:00 AM EDT Reads: 454
WebRTC has had a real tough three or four years, and so have those working with it. Only a few short years ago, the development world were excited about WebRTC and proclaiming how awesome it was. You might have played with the technology a couple of years ago, only to find the extra infrastructure requirements were painful to implement and poorly documented. This probably left a bitter taste in your mouth, especially when things went wrong.
Sep. 5, 2015 07:00 AM EDT Reads: 522