|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
Data is an unusual currency; it is not restricted by the same transactional limitations as money or people. In fact, the more that you leverage your data across multiple business use cases, the more valuable it becomes to the organization. And the same can be said about the organization’s analytics. In his session at 19th Cloud Expo, Bill Schmarzo, CTO for the Big Data Practice at EMC, will introduce a methodology for capturing, enriching and sharing data (and analytics) across the organizati...
Sep. 24, 2016 09:45 PM EDT Reads: 1,594
DevOps at Cloud Expo, taking place Nov 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 19th 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 dev...
Sep. 24, 2016 09:30 PM EDT Reads: 3,317
I'm a lonely sensor. I spend all day telling the world how I'm feeling, but none of the other sensors seem to care. I want to be connected. I want to build relationships with other sensors to be more useful for my human. I want my human to understand that when my friends next door are too hot for a while, I'll soon be flaming. And when all my friends go outside without me, I may be left behind. Don't just log my data; use the relationship graph. In his session at @ThingsExpo, Ryan Boyd, Engi...
Sep. 24, 2016 09:15 PM EDT Reads: 1,192
SYS-CON Events announced today that Secure Channels will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. The bedrock of Secure Channels Technology is a uniquely modified and enhanced process based on superencipherment. Superencipherment is the process of encrypting an already encrypted message one or more times, either using the same or a different algorithm.
Sep. 24, 2016 09:00 PM EDT Reads: 1,412
The vision of a connected smart home is becoming reality with the application of integrated wireless technologies in devices and appliances. The use of standardized and TCP/IP networked wireless technologies in line-powered and battery operated sensors and controls has led to the adoption of radios in the 2.4GHz band, including Wi-Fi, BT/BLE and 802.15.4 applied ZigBee and Thread. This is driving the need for robust wireless coexistence for multiple radios to ensure throughput performance and th...
Sep. 24, 2016 08:30 PM EDT Reads: 1,434
The Internet of Things can drive efficiency for airlines and airports. In their session at @ThingsExpo, Shyam Varan Nath, Principal Architect with GE, and Sudip Majumder, senior director of development at Oracle, will discuss the technical details of the connected airline baggage and related social media solutions. These IoT applications will enhance travelers' journey experience and drive efficiency for the airlines and the airports. The session will include a working demo and a technical d...
Sep. 24, 2016 08:00 PM EDT Reads: 1,645
SYS-CON Events announced today the Enterprise IoT Bootcamp, being held November 1-2, 2016, in conjunction with 19th Cloud Expo | @ThingsExpo at the Santa Clara Convention Center in Santa Clara, CA. Combined with real-world scenarios and use cases, the Enterprise IoT Bootcamp is not just based on presentations but with hands-on demos and detailed walkthroughs. We will introduce you to a variety of real world use cases prototyped using Arduino, Raspberry Pi, BeagleBone, Spark, and Intel Edison. Y...
Sep. 24, 2016 07:00 PM EDT Reads: 2,781
Fact is, enterprises have significant legacy voice infrastructure that’s costly to replace with pure IP solutions. How can we bring this analog infrastructure into our shiny new cloud applications? There are proven methods to bind both legacy voice applications and traditional PSTN audio into cloud-based applications and services at a carrier scale. Some of the most successful implementations leverage WebRTC, WebSockets, SIP and other open source technologies. In his session at @ThingsExpo, Da...
Sep. 24, 2016 06:45 PM EDT Reads: 1,470
If you’re responsible for an application that depends on the data or functionality of various IoT endpoints – either sensors or devices – your brand reputation depends on the security, reliability, and compliance of its many integrated parts. If your application fails to deliver the expected business results, your customers and partners won't care if that failure stems from the code you developed or from a component that you integrated. What can you do to ensure that the endpoints work as expect...
Sep. 24, 2016 04:30 PM EDT Reads: 1,504
Traditional on-premises data centers have long been the domain of modern data platforms like Apache Hadoop, meaning companies who build their business on public cloud were challenged to run Big Data processing and analytics at scale. But recent advancements in Hadoop performance, security, and most importantly cloud-native integrations, are giving organizations the ability to truly gain value from all their data. In his session at 19th Cloud Expo, David Tishgart, Director of Product Marketing ...
Sep. 24, 2016 04:30 PM EDT Reads: 1,695
While DevOps promises a better and tighter integration among an organization’s development and operation teams and transforms an application life cycle into a continual deployment, Chef and Azure together provides a speedy, cost-effective and highly scalable vehicle for realizing the business values of this transformation. In his session at @DevOpsSummit at 19th Cloud Expo, Yung Chou, a Technology Evangelist at Microsoft, will present a unique opportunity to witness how Chef and Azure work tog...
Sep. 24, 2016 04:00 PM EDT Reads: 1,549
Information technology is an industry that has always experienced change, and the dramatic change sweeping across the industry today could not be truthfully described as the first time we've seen such widespread change impacting customer investments. However, the rate of the change, and the potential outcomes from today's digital transformation has the distinct potential to separate the industry into two camps: Organizations that see the change coming, embrace it, and successful leverage it; and...
Sep. 24, 2016 03:00 PM EDT Reads: 1,023
SYS-CON Events announced today that China Unicom will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. China United Network Communications Group Co. Ltd ("China Unicom") was officially established in 2009 on the basis of the merger of former China Netcom and former China Unicom. China Unicom mainly operates a full range of telecommunications services including mobile broadband (GSM, WCDMA, LTE F...
Sep. 24, 2016 01:30 PM EDT Reads: 1,674
Enterprise IT has been in the era of Hybrid Cloud for some time now. But it seems most conversations about Hybrid are focused on integrating AWS, Microsoft Azure, or Google ECM into existing on-premises systems. Where is all the Private Cloud? What do technology providers need to do to make their offerings more compelling? How should enterprise IT executives and buyers define their focus, needs, and roadmap, and communicate that clearly to the providers?
Sep. 24, 2016 01:00 PM EDT Reads: 1,483
SYS-CON Events announced today that SoftLayer, an IBM Company, has been named “Gold Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. SoftLayer, an IBM Company, provides cloud infrastructure as a service from a growing number of data centers and network points of presence around the world. SoftLayer’s customers range from Web startups to global enterprises.
Sep. 24, 2016 12:00 PM EDT Reads: 762