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T-CELL BREAKTHROUGH - I READ THIS TODAY AND WANTED TO PASS IT ALONG.

Holdtight's picture
Holdtight
Posts: 138
Joined: Aug 2009

 

Cancer researchers worldwide are heralding the results of a "sensational" new study, in which a team from the University of Pennsylvania showed that a cancer patient's own immune cells can be genetically re-engineered to target and kill cancer cells. Though it's a preliminary study involving only three patients with leukemia, the successful results have left typically staid medical researchers wildly buoyant. Here, a guide to this breakthrough:

 

How was this study conducted?
Blood samples were drawn from three people with chronic lymphocytic leukemia, an aggressive form of cancer that affects blood and bone marrow. The patients' T cells — a type of immune cell found in the blood — were then genetically re-engineered with a strict agenda: To find cancer cells and kill them. "We put a key onto the surface of the T-cells that fits into a lock that only the cancer cells have," says researcher Dr. Michael Kalos, as quoted in the Vancouver Sun. The modified T cells were then infused back into the patients' blood.

What happened to the patients?
The results were so dramatic, even the doctors were shocked: "Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected," says researcher Carl June. Moreover, these patients' tumors were in an advanced stage, and the prognoses were quite negative. Following the treatment, however, "we saw massive reduction in tumour burden," says Dr. Kalos. "One patient had over seven pounds of tumor and it all disappeared."

 

Could the cancer return?
It's possible. But the modified T cells — which essentially became "serial killers" — proved hearty, growing their numbers more than 1,000 times through reproduction, and surviving for months. Plus, the researchers programmed the cells to produce dormant offspring T cells that would spring back to life if the cancer ever returned.

 

How are the patients doing?
A year after the therapy started, two of the patients had complete remission of leukemia, and one had a partial response to the therapy — the patient's cancer is less severe. One of the patients wrote in a first-person essay, "I'm healthy and still in remission. I know that this may not be a permanent condition, but I decided months ago to declare victory and assume that I had won."

 

Are there any downsides to this new therapy?
Yes. The treatment is so strong that it can result in "tumor lysis syndrome" — chills, nausea, and fever — caused when a large number of cancer cells die very suddenly. Because tumor lysis syndrome can result in kidney failure, the condition requires prompt medical treatment. 

 

What are other cancer researchers saying?
Most are very enthusiastic. "This is a huge accomplishment — huge," says Dr. Lee M. Nadler of Harvard Medical School, as quoted in the Los Angeles Times. Researchers have been struggling for decades to develop cancer treatments that use a patient's immune system to kill tumors with greater precision, leaving the rest of the body unharmed. "It is kind of a holy grail," says Dr. Gary Schiller of UCLA.

 

When will the new therapy be available?
Not for several years, if ever. Much more research needs to be conducted to ensure that this treatment is safe and effective. "The longer term toxicities and efficacy are not at all clear," said Dr. Bruce Chabner of Massachusetts General Hospital Cancer Center, as quoted by ABC News. "[This treatment] could be historic, but it will take several more years and many more cases before we know."

 

Sources: ABC News, CNN.com, LA Times, Medical News Today, Vancouver Sun

ATLANTA — 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.

Related Links

·      Department of Pathology & Laboratory Medicine

·      The Abramson Cancer Center

·      Division of Hematology-Oncology

·      Perelman School of Medicine at the University of Pennsylvania

·      University of Pennsylvania Health System

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, MD, 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, MD, 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 PM in the Thomas Murphy Ballroom 4, Level 5, Building B of the Georgia World Congress Center. Michael Kalos, PhD, 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 PM in C208-C210, Level 2, Building C. Stephan Grupp, MD, PhD, 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 PM 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 note: The University of Pennsylvania has licensed this technology to Novartis. Some of the scientists involved in these trials are inventors of this technology.

lp1964's picture
lp1964
Posts: 856
Joined: Jun 2013

...research at Stanford called CD47 antigen that attacks cancer cells. The human trials will start next summer.

Thank you for posting that amazing article above. And yes, we are holding tight until better cures are found.

Laz

janderson1964's picture
janderson1964
Posts: 1641
Joined: Oct 2011

I read about the research listed above about a year ago but I have been following the CD47 antibody more closely that you mentioned Laz. It seems very promising and is supposed to go into trials mid 2014. I just hope that it is as effective in himans as it is in mice and if so that the FDA takes notice and puts it on the fast track for approval.

herdizziness's picture
herdizziness
Posts: 3402
Joined: Apr 2010

The Stanford trial will only have "10 to 100" participants, I'm hoping more then TEN, when this article came out a bit ago, I said that's the trial I want to be in.  Shame it's such a low amount of participants but here's hoping.  The Stanford trial has worked extremely well in animal testing and they seem very excited about it.  I figure we all just have to keep holding on until they come up with something.  And that too has been something I've been hoping for, that it does well enough to be fast tracked, I keep telling myself keep going something may show up, hoping this is it.

Winter Marie

janderson1964's picture
janderson1964
Posts: 1641
Joined: Oct 2011

That is exactly how I am thinking. I keep telling myself everyday I wake up I am a day closer to a breakthrough. I am not even talking about cure but one drug that can keep it under control like the way they can control most diabetics or prople with HIV.

KathiM's picture
KathiM
Posts: 7879
Joined: Aug 2005

I am 7 years NED from stage III rectal and stage II breast cancer.  I don't fit into any research slot, so I feel a bit frustrated.....why me?

 

My family's immune system is different....we heal VERY easy and fast.  We hardly ever get colds or flu, and if we do, it's very short lived.  We have high aggregate cholesterol, but our ratios are very skewed.....toward the good cholesterol...so none of us take meds to control.   But my mom, sister, and I all have had 2 primary cancers each.  Breast cancer and another.  But, even though they were more advanced stages, we all survived them, becoming NED.  

 

So, I am happy to see all of the attention on the immune system!!!!!  I recently read another excerp about the theory that the reason why some people respond more to a certain chemotherapy regiment than another is that they are more allergic to the certain chemical, and so the immune system gets put on high alert! (I had a severe reaction to Taxol, I even stopped breathing...for a minute or so....).

 

Thank you, again, for posting!!!!

 

Hugs, Kathi

Easyflip's picture
Easyflip
Posts: 108
Joined: May 2013

Fingers crossed, I wonder why they can't fast track these things? Let's hope for the best.

coloCan
Posts: 1850
Joined: Oct 2009
KathiM's picture
KathiM
Posts: 7879
Joined: Aug 2005

Hugs, Kathi

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