Welcome!

News Feed Item

Leukemia Patients Remain in Remission More Than Two Years After Receiving Genetically Engineered T Cell Therapy

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.

(Photo: http://photos.prnewswire.com/prnh/20121209/DC26187)

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

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
Multiple data types are pouring into IoT deployments. Data is coming in small packages as well as enormous files and data streams of many sizes. Widespread use of mobile devices adds to the total. In this power panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists looked at the tools and environments that are being put to use in IoT deployments, as well as the team skills a modern enterprise IT shop needs to keep things running, get a handle on all this data, and deliver...
In his session at @ThingsExpo, Eric Lachapelle, CEO of the Professional Evaluation and Certification Board (PECB), provided an overview of various initiatives to certify the security of connected devices and future trends in ensuring public trust of IoT. Eric Lachapelle is the Chief Executive Officer of the Professional Evaluation and Certification Board (PECB), an international certification body. His role is to help companies and individuals to achieve professional, accredited and worldwide re...
Both SaaS vendors and SaaS buyers are going “all-in” to hyperscale IaaS platforms such as AWS, which is disrupting the SaaS value proposition. Why should the enterprise SaaS consumer pay for the SaaS service if their data is resident in adjacent AWS S3 buckets? If both SaaS sellers and buyers are using the same cloud tools, automation and pay-per-transaction model offered by IaaS platforms, then why not host the “shrink-wrapped” software in the customers’ cloud? Further, serverless computing, cl...
You know you need the cloud, but you’re hesitant to simply dump everything at Amazon since you know that not all workloads are suitable for cloud. You know that you want the kind of ease of use and scalability that you get with public cloud, but your applications are architected in a way that makes the public cloud a non-starter. You’re looking at private cloud solutions based on hyperconverged infrastructure, but you’re concerned with the limits inherent in those technologies.
Wooed by the promise of faster innovation, lower TCO, and greater agility, businesses of every shape and size have embraced the cloud at every layer of the IT stack – from apps to file sharing to infrastructure. The typical organization currently uses more than a dozen sanctioned cloud apps and will shift more than half of all workloads to the cloud by 2018. Such cloud investments have delivered measurable benefits. But they’ve also resulted in some unintended side-effects: complexity and risk. ...
With the introduction of IoT and Smart Living in every aspect of our lives, one question has become relevant: What are the security implications? To answer this, first we have to look and explore the security models of the technologies that IoT is founded upon. In his session at @ThingsExpo, Nevi Kaja, a Research Engineer at Ford Motor Company, discussed some of the security challenges of the IoT infrastructure and related how these aspects impact Smart Living. The material was delivered interac...
The taxi industry never saw Uber coming. Startups are a threat to incumbents like never before, and a major enabler for startups is that they are instantly “cloud ready.” If innovation moves at the pace of IT, then your company is in trouble. Why? Because your data center will not keep up with frenetic pace AWS, Microsoft and Google are rolling out new capabilities. In his session at 20th Cloud Expo, Don Browning, VP of Cloud Architecture at Turner, posited that disruption is inevitable for comp...
It is ironic, but perhaps not unexpected, that many organizations who want the benefits of using an Agile approach to deliver software use a waterfall approach to adopting Agile practices: they form plans, they set milestones, and they measure progress by how many teams they have engaged. Old habits die hard, but like most waterfall software projects, most waterfall-style Agile adoption efforts fail to produce the results desired. The problem is that to get the results they want, they have to ch...
IoT solutions exploit operational data generated by Internet-connected smart “things” for the purpose of gaining operational insight and producing “better outcomes” (for example, create new business models, eliminate unscheduled maintenance, etc.). The explosive proliferation of IoT solutions will result in an exponential growth in the volume of IoT data, precipitating significant Information Governance issues: who owns the IoT data, what are the rights/duties of IoT solutions adopters towards t...
"We are a monitoring company. We work with Salesforce, BBC, and quite a few other big logos. We basically provide monitoring for them, structure for their cloud services and we fit into the DevOps world" explained David Gildeh, Co-founder and CEO of Outlyer, in this SYS-CON.tv interview at DevOps Summit at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
In 2014, Amazon announced a new form of compute called Lambda. We didn't know it at the time, but this represented a fundamental shift in what we expect from cloud computing. Now, all of the major cloud computing vendors want to take part in this disruptive technology. In his session at 20th Cloud Expo, Doug Vanderweide, an instructor at Linux Academy, discussed why major players like AWS, Microsoft Azure, IBM Bluemix, and Google Cloud Platform are all trying to sidestep VMs and containers wit...
While DevOps most critically and famously fosters collaboration, communication, and integration through cultural change, culture is more of an output than an input. In order to actively drive cultural evolution, organizations must make substantial organizational and process changes, and adopt new technologies, to encourage a DevOps culture. Moderated by Andi Mann, panelists discussed how to balance these three pillars of DevOps, where to focus attention (and resources), where organizations might...
"When we talk about cloud without compromise what we're talking about is that when people think about 'I need the flexibility of the cloud' - it's the ability to create applications and run them in a cloud environment that's far more flexible,” explained Matthew Finnie, CTO of Interoute, in this SYS-CON.tv interview at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
The Internet giants are fully embracing AI. All the services they offer to their customers are aimed at drawing a map of the world with the data they get. The AIs from these companies are used to build disruptive approaches that cannot be used by established enterprises, which are threatened by these disruptions. However, most leaders underestimate the effect this will have on their businesses. In his session at 21st Cloud Expo, Rene Buest, Director Market Research & Technology Evangelism at Ara...
No hype cycles or predictions of zillions of things here. IoT is big. You get it. You know your business and have great ideas for a business transformation strategy. What comes next? Time to make it happen. In his session at @ThingsExpo, Jay Mason, Associate Partner at M&S Consulting, presented a step-by-step plan to develop your technology implementation strategy. He discussed the evaluation of communication standards and IoT messaging protocols, data analytics considerations, edge-to-cloud tec...