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HIV Vector Licks Leukemia
Genetic Engineering & Biotechnology News ^ | Dec 10, 2012 | NA

Posted on 12/10/2012 6:20:25 PM PST by neverdem

A gene therapy that uses infusions of patients’ own T cells genetically engineered to attack their tumors enjoyed its first successful and sustained demonstration of clinical-trial success in nine of 12 leukemia patients—two of whom have been in remission for more than two years.

The therapy was pioneered by the University of Pennsylvania’s Perelman School of Medicine, whose researchers will present latest results from the study today at the American Society of Hematology (ASH)'s Annual Meeting and Exposition in Atlanta.

According to Penn Perelman, 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. Transplantations require lengthy hospitalizations and carry at least a 20% mortality risk, with only a limited chance of cure for patients whose disease has not responded to other treatments.

“Chimeric antigen receptor-modified T cells have great promise to improve the treatment of leukemia and lymphoma," 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 new treatment uses an apheresis process similar to blood donation to remove patients' cells, then modify them in Penn's cell and vaccine production facility. There, scientists apply a gene modification technique to target tumor cells by reprogramming patients' T cells using a HIV-derived lentivirus vector. The vector encodes a chimeric antigen receptor (CAR), an antibody-like protein expressed on the surface of the T cells, and designed to bind to the protein CD19.

Modified cells are infused back into the patient's body following lymphodepleting chemotherapy. Once 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 other cells are ignored by the modified T cells, thus limiting the side effects typically experienced during traditional therapies.

A signaling molecule built into the CAR also spurs the cell to produce cytokines that trigger other T cells to multiply until all target cells in the tumor are destroyed.

In patients experiencing complete remissions after treatment, CAR T cells exhibited vigorous proliferation after infusion, with the strongest 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 with tocilizumab.

Ultimately, the modified T-cell treatment eradicated large amounts of tumors in these patients, as well as normal B cells used by the body's immune system to fight infection. Patients were given regular gamma globulin treatments as a preventive measure.

Clinical trial participants included 10 adult patients with chronic lymphocytic leukemia treated at the Hospital of the University of Pennsylvania, and two children with acute lymphoblastic leukemia treated at the Children's Hospital of Philadelphia.

At the ASH annual meeting, abstracts about the new research will be presented later today by David Porter, M.D., director of blood and marrow transplantation in the Abramson Cancer Center; Michael Kalos, Ph.D., director of the translational and correlative studies laboratory at Penn; and Stephan Grupp, M.D., Ph.D., director of translational research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia.


TOPICS: Crime/Corruption; Culture/Society; News/Current Events; Testing
KEYWORDS: cancer; genetherapy; hivaids; immunology; immunotherapies; leukemia

1 posted on 12/10/2012 6:20:33 PM PST by neverdem
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To: neverdem

What a wonderful day for the memory of Janis Babson

2 posted on 12/10/2012 6:34:58 PM PST by Slyfox (The key to Marxism is medicine - V. Lenin)
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>> to produce cytokines that trigger other T cells to multiply until all target cells in the tumor are destroyed.

The perfect cytokine storm...

>> using a HIV-derived lentivirus vector.

Lentivirus: any of a group of retroviruses producing illnesses characterized by a delay in the onset of symptoms after infection. /oxford


3 posted on 12/10/2012 6:47:06 PM PST by Gene Eric (Demoralization is a weapon of the enemy. Don't get it, don't spread it!)
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To: neverdem

bookmark


4 posted on 12/10/2012 7:01:52 PM PST by southland ( party will lead us)
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To: neverdem
This looks like the same story XKCD had a little fun with last year.


5 posted on 12/10/2012 7:09:07 PM PST by KarlInOhio (Big Bird is a brood parasite: laid in our nest 43 years ago and we are still feeding him.)
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To: KarlInOhio; southland; Gene Eric; Slyfox; Mother Abigail; EBH; vetvetdoug; Smokin' Joe; ...
The technique employs a disabled form of HIV because it is very good at carrying genetic material into T-cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turns malignant in leukemia.

The Globe and Mail reposted this NY Times story. I wanted to know how they disabled HIV. HIV and CD-19 and leukemia got nothing at PubMed.

Attenuated HIV and disabled HIV was just as useless as an effective search strategy.

6 posted on 12/11/2012 5:59:18 PM PST by neverdem ( Xin loi min oi)
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To: neverdem

Have a lot of questions about this one.


7 posted on 12/11/2012 8:19:19 PM PST by Irish Eyes
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To: neverdem
Ultimately, the modified T-cell treatment eradicated large amounts of tumors in these patients, as well as normal B cells used by the body's immune system to fight infection. Patients were given regular gamma globulin treatments as a preventive measure.

Ohhhh kay.

If the immune system is wiped out by the modified T-cells, doesn't that leave the patient with an acquired immunodeficiency?

How is that addressed over the long term?

Or have they just not got that far...

8 posted on 12/12/2012 7:29:41 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: 2ndreconmarine; Fitzcarraldo; Covenantor; Mother Abigail; EBH; Dog Gone; ...

Ping... (Thanks, neverdem!)


9 posted on 12/12/2012 7:40:44 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: 2ndreconmarine; Fitzcarraldo; Covenantor; Mother Abigail; EBH; Dog Gone; ...

Ping... (Thanks, neverdem!)


10 posted on 12/12/2012 7:41:26 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: neverdem

Hmm...

Something smells bad.


11 posted on 12/12/2012 11:12:48 AM PST by redgolum ("God is dead" -- Nietzsche. "Nietzsche is dead" -- God.)
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To: Smokin' Joe
**************************************EXCERPTS**************************************

Each of these patients developed a cytokine release syndrome—marked by fever, nausea, hypoxia, and low blood pressure—which doctors treated with tocilizumab.

********************************************************

and

**********************************************

..... as well as normal B cells used by the body's immune system to fight infection. Patients were given regular gamma globulin treatments as a preventive measure.

12 posted on 12/12/2012 11:14:43 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: neverdem
From the linked article:

**************************************EXCERPT*****************************************

A major drug company, Novartis, is betting on the Pennsylvania team and has committed $20-million to building a research centre on the university’s campus to bring the treatment to market.

13 posted on 12/12/2012 11:26:13 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: redgolum

Why?


14 posted on 12/12/2012 11:27:40 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: Ernest_at_the_Beach

What I am asking is: Does the Gamma Globulin treatment restore (or does the body recover) B cell production/levels, or does the change persist?


15 posted on 12/12/2012 11:30:07 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: neverdem
Here is the snippet I am looking for.....

************************************EXCERPT******************************************

Researchers say the same approach, reprogramming the patient’s immune system, may also be used eventually against tumours like breast and prostate cancer.

16 posted on 12/12/2012 11:35:19 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: Smokin' Joe

Oh,...damn good question.


17 posted on 12/12/2012 11:36:57 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: Ernest_at_the_Beach

Mrs. (Dr.) Jewbacca always has told me that the true secret to all cancers is getting the body to attack the cancer cells.

This is both “hugh” and “series.”

Unfortunate that it is a “T-Virus.” Sounds like that movie where everyone turns into zombies.


18 posted on 12/12/2012 11:38:24 AM PST by Jewbacca (The residents of Iroquois territory may not determine whether Jews may live in Jerusalem.)
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To: Smokin' Joe
Novartis: Broad healthcare portfolio for changing patient needs
www.novartis.com/Cached - Similar
You +1'd this publicly. Undo
We want to discover, develop and successfully market innovative products to prevent and cure diseases, to ease suffering and to enhance the quality of life.
Google+ page
26516 Maside  Mission Viejo, CA 92692
(949) 582-7198

19 posted on 12/12/2012 11:39:12 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: Jewbacca; neverdem; Smokin' Joe
Novartis may be a company to watch.....some news:

Novartis to start construction of new biotechnology facility in Singapore with an investment of over USD 500 million

20 posted on 12/12/2012 11:50:34 AM PST by Ernest_at_the_Beach ((The Global Warming Hoax was a Criminal Act....where is Al Gore?))
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To: Smokin' Joe; Irish Eyes; redgolum; El Gato; Ernest_at_the_Beach; Robert A. Cook, PE; lepton; ...
"Ultimately, the modified T-cell treatment eradicated large amounts of tumors in these patients, as well as normal B cells used by the body's immune system to fight infection. Patients were given regular gamma globulin treatments as a preventive measure."

Ohhhh kay.

If the immune system is wiped out by the modified T-cells, doesn't that leave the patient with an acquired immunodeficiency?

Only part of the adaptive immune system was attacked. Those B lymphocytes confer humoral immunity by making antibodies to foreign pathogens.

Log or Exponential Phase
In this phase, the antibody concentration increases exponentially as the B cells that were stimulated by the antigen differentiate into plasma cells which secrete antibody.

They still have cell mediated immunity courtesy of T lymphocytes and the primitive innate immune system. They directed the attack to leukemic cells expressing CD19. CD stands for cluster of differentiation.

Unfortunately, CD19 is also expressed on B cells, also known as B lymphocytes.

How is that addressed over the long term?

"Patients were given regular gamma globulin treatments as a preventive measure."

That's a "protein fraction of blood serum containing many antibodies that protect against bacterial and viral infectious diseases." It's periodical. I don't know how frequently. It's not cheap. It comes from donated blood. It must be screened for microbes, etc.

Besides being impressive immunologically, somebody did some impressive molecular genetics on HIV to get a knock out version of HIV. They got one or more serious genetic deletions, or the equivalent, how I don't know, in this "disabled" HIV, or these docs are guilty of assault and battery plus attempted murder!

Any corrections are always appreciated. Just don't tell me HIV isn't a lethal pathogen. Koch's postulates have been fulfilled.

21 posted on 12/12/2012 2:56:45 PM PST by neverdem ( Xin loi min oi)
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To: Smokin' Joe; Irish Eyes; redgolum; El Gato; Ernest_at_the_Beach; Robert A. Cook, PE; lepton; ...
"Ultimately, the modified T-cell treatment eradicated large amounts of tumors in these patients, as well as normal B cells used by the body's immune system to fight infection. Patients were given regular gamma globulin treatments as a preventive measure."

Ohhhh kay.

If the immune system is wiped out by the modified T-cells, doesn't that leave the patient with an acquired immunodeficiency?

Only part of the adaptive immune system was attacked. Those B lymphocytes confer humoral immunity by making antibodies to foreign pathogens.

Log or Exponential Phase
In this phase, the antibody concentration increases exponentially as the B cells that were stimulated by the antigen differentiate into plasma cells which secrete antibody.

They still have cell mediated immunity courtesy of T lymphocytes and the primitive innate immune system. They directed the attack to leukemic cells expressing CD19. CD stands for cluster of differentiation.

Unfortunately, CD19 is also expressed on B cells, also known as B lymphocytes.

How is that addressed over the long term?

"Patients were given regular gamma globulin treatments as a preventive measure."

That's a "protein fraction of blood serum containing many antibodies that protect against bacterial and viral infectious diseases." It's periodical. I don't know how frequently. It's not cheap. It comes from donated blood. It must be screened for microbes, etc.

Besides being impressive immunologically, somebody did some impressive molecular genetics on HIV to get a knock out version of HIV. They got one or more serious genetic deletions, or the equivalent, how I don't know, in this "disabled" HIV, or these docs are guilty of assault and battery plus attempted murder!

Any corrections are always appreciated. Just don't tell me HIV isn't a lethal pathogen. Koch's postulates have been fulfilled.

22 posted on 12/12/2012 2:57:43 PM PST by neverdem ( Xin loi min oi)
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To: Smokin' Joe

Thanks for the ping!


23 posted on 12/12/2012 10:02:25 PM PST by Alamo-Girl
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To: neverdem

I pray this successfully gets out of clinical trials.


24 posted on 12/12/2012 10:18:13 PM PST by <1/1,000,000th%
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To: Alamo-Girl

You’re Welcome, Alamo-Girl!


25 posted on 12/13/2012 2:49:21 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: Smokin' Joe
Cost-effectiveness of splenectomy versus intravenous gamma globulin in treatment of chronic immune thrombocytopenic purpura in childhood

Each additional life saved by employing the IVGG strategy cost $540,000, or $8,000 per year for a life expectancy of 70 years.

Those numbers are over 24 years old. IVGG means intravenous gamma globulin.

I tried calling a local hospital. I got nowhere fast. My BIL is a pharmacist. I left a message. Maybe he can find out more current numbers.

26 posted on 12/13/2012 12:56:37 PM PST by neverdem ( Xin loi min oi)
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