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Collaboration is the critical ingredient in cell therapy

Collaboration is the critical ingredient in cell therapy | cell-based therapy | Scoop.it
There’s a one word answer to removing bottlenecks identified in the recent House of Lords report on translating stem cell science into effective therapies, and that’s Collaboration.
Nancy Parenteau's insight:

Even if you can put together a powerful collaboration, the underlying issue I see with academic efforts is the perisitent focus on individual career needs of the collaborators.  While collaboration will likely produce better quality (less naîve) publications, I wonder if collaboration will be enough to stop the trend of stem cell therapy research repeatedly falling short of addressing the really pressing questions that will either enable or eliminate possibilities for cell therapies.

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T-Cell Therapy Eradicates an Aggressive Leukemia in Two Children

T-Cell Therapy Eradicates an Aggressive Leukemia in Two Children | cell-based therapy | Scoop.it

Two children with an aggressive form of childhood leukemia had a complete remission of their disease—showing no evidence of cancer cells in their bodies—after treatment with a novel cell therapy that reprogrammed their immune cells to rapidly multiply and destroy leukemia cells. A research team from The Children’s Hospital of Philadelphia and the University of Pennsylvania published the case report of two pediatric patients Online First today in The New England Journal of Medicine. It will appear in the April 18 print issue.

 

The current study builds on Grupp’s ongoing collaboration with Penn Medicine scientists who originally developed the modified T cells as a treatment for B-cell leukemias. The Penn team reported on early successful results of a trial using this cell therapy in three adult chronic lymphocytic leukemia (CLL) patients in August of 2011. Two of those patients remain in remission more than 2½ years following their treatment, and as the Penn researchers reported in December 2012 at the annual meeting of the American Society of Hematology, seven out of ten adult patients treated at that point responded to the therapy. The team is led by the current study’s senior author, Carl H. June, M.D., the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and the Perelman School of Medicine at the University of Pennsylvania and director of Translational Research in Penn’s Abramson Cancer Center.

 

“We’re hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations,” June said. “In the long run, if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy.”

 

The research team colleagues adapted the original CLL treatment to combat another B-cell leukemia: ALL, which is the most common childhood cancer. After decades of research, oncologists can currently cure 85 percent of children with ALL. Both children in the current study had a high-risk type of ALL that stubbornly resists conventional treatments.

The new study used a relatively new approach in cancer treatment: immunotherapy, which manipulates the immune system to increase its cancer-fighting capabilities. Here the researchers engineered T cells to selectively kill another type of immune cell called B cells, which had become cancerous.

 

The researchers removed some of each patient’s own T cells and modified them in the laboratory to create a type of CAR (chimeric antigen receptor) cell called a CTL019 cell. These cells are designed to attack a protein called CD19 that occurs only on the surface of certain B cells.

 

By creating an antibody that recognizes CD19 and then connecting that antibody to T cells, the researchers created in CTL019 cells a sort of guided missile that locks in on and kills B cells, thereby attacking B-cell leukemia. After being returned to the patient’s body, the CTL019 cells multiply a thousand times over and circulate throughout the body. Importantly, they persist for months afterward, guarding against a recurrence of this specific type of leukemia.

 

While the CTL019 cells eliminate leukemia, they also can generate an overactive immune response, called a cytokine release syndrome, involving dangerously high fever, low blood pressure, and other side effects. This complication was especially severe in Emily, and her hospital team needed to provide her with treatments that rapidly relieved the treatment-related symptoms by blunting the immune overresponse, while still preserving the modified T cells’ anti-leukemia activity.

 

“The comprehensive testing plan that we have put in place to study patients’ blood and bone marrow while they’re undergoing this therapy is allowing us to be able to follow how the T cells are behaving in patients in real time, and guides us to be able to design more detailed and specific experiments to answer critical questions that come up from our studies,” Kalos said.

 

The CTL019 therapy eliminates all B cells that carry the CD19 cell receptor: healthy cells as well as those with leukemia. Patients can live without B cells, although they require regular replacement infusions of immunoglobulin, which can be given at home, to perform the immune function normally provided by B cells.

 

The research team continues to refine their approach using this new technology and explore reasons why some patients may not respond to the therapy or may experience a recurrence of their disease. Grupp said the appearance of the CD19-negative leukemia cells in the second child may have resulted from her prior treatments. Unlike Emily, the second patient had received an umbilical cord cell transplant from a matched donor, so her engineered T cells were derived from her donor (transplanted) cells, with no additional side effects. Oncologists had previously treated her with blinatumomab, a monoclonal antibody, in hopes of fighting the cancer. The prior treatments may have selectively favored a population of CD19-negative T cells.

 

“The emergence of tumor cells that no longer contain the target protein suggests that in particular patients with high-risk ALL, we may need to broaden the treatment to include additional T cells that may go after additional targets,” added Grupp. “However, the initial results with this immune-based approach are encouraging, and may later even be developed into treatments for other types of cancer.”


Via Dr. Stefan Gruenwald
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Soumya Rao's comment, May 1, 2013 5:17 AM
Wow... really amazing!!! Hope it transforms lives soon...
Nacho Vega's curator insight, May 1, 2013 1:58 PM

YES we CAN!!!

Nacho Vega's comment, May 1, 2013 2:02 PM
YES we CAN!
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Don't market stem-cell products ahead of proof - Nature.com

Don't market stem-cell products ahead of proof - Nature.com | cell-based therapy | Scoop.it
Don't market stem-cell products ahead of proof
Nature.com
Mesenchymal stem cells (MSCs) provide a prime example of this.
Nancy Parenteau's insight:

Pushing to commercialize a cell therapy without adequate science and development is ultimately a lose-lose proposition.  The science continues to suffer from lack of rigor and adequate attention to what is truly pivotal for success; the therapy never advances to a meaningful outcome; patients loose their money, and ironically, a substantial delay in recieiving a therapy that really could really help them.  

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Stem-Cell Heart Repair Questioned. Why you shouldn't believe everything you read.

Stem-Cell Heart Repair Questioned.  Why you shouldn't believe everything you read. | cell-based therapy | Scoop.it
A new analysis finds hundreds of discrepancies in publications from a German researcher who claims to have repaired diseased hearts using stem-cell therapy.
 

Via Richard D. Hammer, M.D.
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Richard D. Hammer, M.D.'s curator insight, July 13, 2013 10:28 AM

A set back for sure.  Evaluating studies takes experience and knowledge.  Many published studies are poorly done and have flaws.  Claims are sensationalized by the media and accepted as truth without a rigourous evaluation.

Such was the case with the NIH Womens Health Initiative Study which incorrectly impacted horomone use in women until recent re-evaluation.  Many reviews of the incorrect and overblown conclusions are available.  Yet the impact over a 10 year period was tremendous, decreasing hormone use by 71% and precluding the potential benefits to a large group of women.  

 

While this may not be of the same impact, it is certainly a set back in understanding the use of stem cells.  I firmly believe the future of medicine is in stem cell and cellular therapies.  This doesn't help us get there.

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Lynsie Conradi's Leukemia Clears Up After Experimental Cancer ...

Lynsie Conradi's Leukemia Clears Up After Experimental Cancer ... | cell-based therapy | Scoop.it
This experimental form of treatment, also known as T-Cell therapy, entails removing a sample of the patient's blood in order to rewire "infection-fighting" T-cells so that they are better equipped to fend off cancerous cells.
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