Gene Therapy Showing Increasing Promise

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Gene Therapy Showing Increasing Promise

 

Genetically Modified 'Serial Killer' T-Cells Obliterate Tumors in Leukemia Patients

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The protocol, which involves removing patients' cells and modifying them in Penn's vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy, provides a tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma. (Credit: Image courtesy of University of Pennsylvania School of Medicine)

ScienceDaily (Aug. 10, 2011) — In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania's Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells. The protocol, which involves removing patients' cells and modifying them in Penn's vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy, provides a tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma.

 

The findings, published simultaneously in the New England Journal of Medicine and Science Translational Medicine on August 10, are the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors.

"Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected," said senior author Carl June, MD, director of Translational Research and a professor of Pathology and Laboratory Medicine in the Abramson Cancer Center, who led the work. "It worked much better than we thought it would."

The results of the pilot trial of three patients are a stark contrast to existing therapies for CLL. The patients involved in the new study had few other treatment options. The only potential curative therapy would have involved a bone marrow transplant, a procedure which requires a lengthy hospitalization and carries at least a 20 percent mortality risk -- and even then offers only about a 50 percent chance of a cure, at best.

"Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them," says co-principal investigator David Porter, MD, professor of Medicine and director of Blood and Marrow Transplantation. "This approach has the potential to do the same thing, but in a safer manner."

Secret Ingredients

June thinks there were several "secret ingredients" that made the difference between the lackluster results that have been seen in previous trials with modified T cells and the remarkable responses seen in the current trial. The details of the new cancer immunotherapy are detailed in Science Translational Medicine.

After removing the patients' cells, the team reprogrammed them to attack tumor cells by genetically modifying them using a 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.

Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL 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 side effects typically experienced during standard therapies.

The team engineered a signaling molecule into the part of the CAR that resides inside the cell. When it binds to CD19, initiating the cancer-cell death, it also tells 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.

Serial Killers

"We saw at least a 1000-fold increase in the number of modified T cells in each of the patients. Drugs don't do that," June says. "In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell led to the killing of thousands of tumor cells -- and overall, destroyed at least two pounds of tumor in each patient."

The importance of the T cell self-replication is illustrated in the New England Journal of Medicine paper, which describes the response of one patient, a 64-year old man. Prior to his T cell treatment, his blood and marrow were replete with tumor cells. For the first two weeks after treatment, nothing seemed to change. Then on day 14, the patient began experiencing chills, nausea, and increasing fever, among other symptoms. Tests during that time showed an enormous increase in the number of T cells in his blood that led to a tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.

By day 28, the patient had recovered from the tumor lysis syndrome -- and his blood and marrow showed no evidence of leukemia.

"This massive killing of tumor is a direct proof of principle of the concept," Porter says.

The Penn team pioneered the use of the HIV-derived vector in a clinical trial in 2003 in which they treated HIV patients with an antisense version of the virus. That trial demonstrated the safety of the lentiviral vector used in the present work.

The cell culture methods used in this trial reawaken T cells that have been suppressed by the leukemia and stimulate the generation of so-called "memory" T cells, which the team hopes will provide ongoing protection against recurrence. Although long-term viability of the treatment is unknown, the doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their seek-and-destroy mission against cancerous cells throughout the patients' bodies.

Moving forward, the team plans to test the same CD19 CAR construct in patients with other types of CD19-positive tumors, including non-Hodgkin's lymphoma and acute lymphocytic leukemia. They also plan to study the approach in pediatric leukemia patients who have failed standard therapy. Additionally, the team has engineered a CAR vector that binds to mesothelin, a protein expressed on the surface of mesothelioma cancer cells, as well as on ovarian and pancreatic cancer cells.

In addition to June and Porter, co-authors on the NEJM paper include Bruce Levine, Michael Kalos, and Adam Bagg, all from Penn Medicine. Michael Kalos and Bruce Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include June, Porter, Sharyn Katz and Adam Bagg from Penn and Stephan Grupp the Children's Hospital of Philadelphia.

The work was supported by the Alliance for Cancer Gene Therapy, a foundation started by Penn graduates, Barbara and Edward Netter, to promote gene therapy research to treat cancer, and the Leukemia & Lymphoma Society.

"Experiments are the only means of knowledge at our disposal. The rest is poetry, imagination." Max Planck


cj
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I saw a slightly different

I saw a slightly different article on this subject and was thinking of TGBaker - hope he is doing well.  Don't know if this research would apply to his case or not.  But I hope he is doing well.

 

-- I feel so much better since I stopped trying to believe.

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"If death isn't sweet oblivion, I will be severely disappointed" - Ruth M.


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Yeah

 

 

he crosses my mind a bit, too. The attraction of this therapy is that it operates at the cellular level - the level cancer operates. The idea of body's immune system being supercharged sounds a lot better than attempting to poison cells inside a living body. 

"Experiments are the only means of knowledge at our disposal. The rest is poetry, imagination." Max Planck


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 I am continually amazed by

 I am continually amazed by the fantastic work of medical researchers. Yet another example of how the relentless pursuit of knowledge benefits our lives. 


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It is indeed so true, and

It is indeed so true, and reinforced with every such advance in our scientific understanding, that the reality of the 'workings' of the real world will continue to surprise us. Yet still no evidence whatever, at least to me, of the 'hand' of a 'designer' at work. Real 'design', and I speak as one involved in both electronic circuit and software design for decades, leads to things which are far more simple, no more complex than they need be, targeted at some specific functionality.

Whereas the intricacies of the interactions, at all levels, from the molecular, cellular, organ, organism, and group level is fascinating, all with no more 'purpose' than perpetuating the processes, in the metaphorical Darwinian sense, as of Dawkin's 'selfish gene', speak to me of the spontaneous emergence of complexity.

The 'Order out of Chaos' described in the now classic book by Ilya Prigogine & Isabelel Stengers, which I just stumbled across in searching through my pile.

Favorite oxymorons: Gospel Truth, Rational Supernaturalist, Business Ethics, Christian Morality

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Hi STOP, PUT YOUR HAND UP!!!

Hi, STOP, PUT YOUR HANDS UP.

What you really need is Jean Therapy and submit to the Lord and Saviour Jesus Christ. This has shown promising effects. Jesus Christ is the only person you and via the Holy Spirit to counsel you.

My play on words are funny. Come on, Drop your weapon.

Respectfully,

Jean Chauvin (Jude 3).

A Rational Christian of Intelligence (rare)with a valid and sound justification for my epistemology and a logical refutation for those with logical fallacies and false worldviews upon their normative of thinking in retrospect to objective normative(s). This is only understood via the imago dei in which we all are.

Respectfully,

Jean Chauvin (Jude 3).


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Ah, Exhibit One in the case

Ah, Exhibit One in the case for the mind-rotting effects of the ultimately illogical belief in God returns.

Whose every post drips with the arrogance of ignorance...

We need you here to demonstrate just how bad the effects of some versions of superstitious belief can be.

Hi Jean.

 

Favorite oxymorons: Gospel Truth, Rational Supernaturalist, Business Ethics, Christian Morality

"Theology is now little more than a branch of human ignorance. Indeed, it is ignorance with wings." - Sam Harris

The path to Truth lies via careful study of reality, not the dreams of our fallible minds - me

From the sublime to the ridiculous: Science -> Philosophy -> Theology


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BobSpence1 wrote:Ah, Exhibit

BobSpence1 wrote:

Ah, Exhibit One in the case for the mind-rotting effects of the ultimately illogical belief in God returns.

Whose every post drips with the arrogance of ignorance...

We need you here to demonstrate just how bad the effects of some versions of superstitious belief can be.

Hi Jean.

 

Bobspence, you are the new Master of Understatement. But you do bring up and interesting point to consider. Are you saying that Jean up there would be any less antisocial, condescending, and verbally abusive without the supposed influence of religion? Because I suggest a personality like his would simply find another avenue for his cynical behavior and attitude towards someone not of his way of thinking.

“A meritocratic society is one in which inequalities of wealth and social position solely reflect the unequal distribution of merit or skills amongst human beings, or are based upon factors beyond human control, for example luck or chance. Such a society is socially just because individuals are judged not by their gender, the colour of their skin or their religion, but according to their talents and willingness to work, or on what Martin Luther King called 'the content of their character'. By extension, social equality is unjust because it treats unequal individuals equally.” "Political Ideologies" by Andrew Heywood (2003)


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Hey Bob

You know you love me. You can't deny this. And if you wanna commit ad hominems abusive, then i would encourage that since this is consistent athesim.

I defeated you bob on empiriicsm and ever since you've been a poor loser. Which is also encouraged, atheism, yeah.

But the real issue here is that your intimidated of my super brain lol. Yeah. No atheist on here has won an argument with me or has gotten away with any foolish argument. I'm an intellectual rambo, and yeah, in terms of logic, you're dead.

Respectfully,

Jean Chauvin (Jude 3).

A Rational Christian of Intelligence (rare)with a valid and sound justification for my epistemology and a logical refutation for those with logical fallacies and false worldviews upon their normative of thinking in retrospect to objective normative(s). This is only understood via the imago dei in which we all are.

Respectfully,

Jean Chauvin (Jude 3).


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Jean Chauvin wrote:You know

Jean Chauvin wrote:

You know you love me. You can't deny this. And if you wanna commit ad hominems abusive, then i would encourage that since this is consistent athesim.

I defeated you bob on empiriicsm and ever since you've been a poor loser. Which is also encouraged, atheism, yeah.

But the real issue here is that your intimidated of my super brain lol. Yeah. No atheist on here has won an argument with me or has gotten away with any foolish argument. I'm an intellectual rambo, and yeah, in terms of logic, you're dead.

Respectfully,

Jean Chauvin (Jude 3).

Might I offer you, Gimpy, an alternative dick therapy. In that, I cram my erect phallus so far down your gullet that you choke on it, and die.

“A meritocratic society is one in which inequalities of wealth and social position solely reflect the unequal distribution of merit or skills amongst human beings, or are based upon factors beyond human control, for example luck or chance. Such a society is socially just because individuals are judged not by their gender, the colour of their skin or their religion, but according to their talents and willingness to work, or on what Martin Luther King called 'the content of their character'. By extension, social equality is unjust because it treats unequal individuals equally.” "Political Ideologies" by Andrew Heywood (2003)


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Jean Chauvin wrote:You know

Jean Chauvin wrote:

You know you love me. You can't deny this. And if you wanna commit ad hominems abusive, then i would encourage that since this is consistent athesim.

I defeated you bob on empiriicsm and ever since you've been a poor loser. Which is also encouraged, atheism, yeah.

But the real issue here is that your intimidated of my super brain lol. Yeah. No atheist on here has won an argument with me or has gotten away with any foolish argument. I'm an intellectual rambo, and yeah, in terms of logic, you're dead.

Respectfully,

Jean Chauvin (Jude 3).

Awwww, Jean you're so cute when you attempt to be condescending....

Instead you simply further reveal the depth of your delusion.

Your inability/unwillingness to even begin to understand how pathetic your 'refutations' and counter-arguments were and your utter failure to grasp the reality of the range and nature of atheist perspectives are almost sad. I would look on it as sad if you weren't so arrogant in your strange alternate universe of discourse.

Not to mention your total incomprehension of the way people like myself and professional researchers pursue the truth 'revealed' by the rigorous application of logic, math, and other deductive systems to empirically derived data, in the continuing iterative process of study, hypothesis, and testing that is Science.

Oh, and welcome back anyway. I (almost) missed ya.

Favorite oxymorons: Gospel Truth, Rational Supernaturalist, Business Ethics, Christian Morality

"Theology is now little more than a branch of human ignorance. Indeed, it is ignorance with wings." - Sam Harris

The path to Truth lies via careful study of reality, not the dreams of our fallible minds - me

From the sublime to the ridiculous: Science -> Philosophy -> Theology


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Hey Bob

Hi Bob,

Listening to Rod Stewart Hot Legs. Good songs.

Of course you missed me. I'm godfather for all atheists.

but honestly, Bob, come one. You were mixing the Rationalism of Descartes with the Empiricism of Hume lol. You know it. There's no getting around this.

Yeah i missed you guys too. I really would like to invite all you over to a barbee. Just leave weapons at home.

But here's a warning to you and all the other atheists. I hope you have an umbrella cause there's gonna be some cold hard facts up all in here.

San Francisco Faggot, um, what? You have the hots for me? What just happen?

Respectfully,

Jean Chauvin (Jude 3).

A Rational Christian of Intelligence (rare)with a valid and sound justification for my epistemology and a logical refutation for those with logical fallacies and false worldviews upon their normative of thinking in retrospect to objective normative(s). This is only understood via the imago dei in which we all are.

Respectfully,

Jean Chauvin (Jude 3).


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p { margin-bottom: 0.08in; }

p { margin-bottom: 0.08in; }

Jean, he is not from San Fransisco. Not even the west coast. And he has never mentioned anything about gay before, so most likely he is willing to make an exception just to see you chock on dick and die.

NoMoreCrazyPeople wrote:
Never ever did I say enything about free, I said "free."

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Answers in Gene Simmons

Answers in Gene Simmons wrote:

p { margin-bottom: 0.08in; }

Jean, he is not from San Fransisco. Not even the west coast. And he has never mentioned anything about gay before, so most likely he is willing to make an exception just to see you chock on dick and die.

 

Laughing out loud

....bon appetit!

“A meritocratic society is one in which inequalities of wealth and social position solely reflect the unequal distribution of merit or skills amongst human beings, or are based upon factors beyond human control, for example luck or chance. Such a society is socially just because individuals are judged not by their gender, the colour of their skin or their religion, but according to their talents and willingness to work, or on what Martin Luther King called 'the content of their character'. By extension, social equality is unjust because it treats unequal individuals equally.” "Political Ideologies" by Andrew Heywood (2003)


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Hello

Hello,

When did Irrational Response Squad become a gay bar? lol. Answers in Genesis, i thought we were friends. You told me you were high in teh occult then i asked you about it and you're like scary cat lol. I Mean, if you were really as high as you say i guess i would understand. But you would have to be a member of the Council of Druids or the 13 familes to be that high. I suppose if you were of the AMORC 6th that would be a little nerve wracking.

But i highly doubt you were that high. You were probably just a solitare nobody.

But let's be friends. And i know being a fag is consistent atheism, but try to be a Chrisitan on this one at least sometimes.

Respectfully,

Jean Chauvin (Jude 3).

A Rational Christian of Intelligence (rare)with a valid and sound justification for my epistemology and a logical refutation for those with logical fallacies and false worldviews upon their normative of thinking in retrospect to objective normative(s). This is only understood via the imago dei in which we all are.

Respectfully,

Jean Chauvin (Jude 3).


HumanVuvuzela
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Jean Chauvin wrote:And i

Jean Chauvin wrote:

And i know being a fag is consistent atheism, but try to be a Chrisitan on this one at least sometimes.

 

Yeah, much better to be a REAL christian and sodomise altar boys. 

 


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JC,you are a fascinating

JC,

you are a fascinating case study in irrationality.

The demonstrated existence, especially via this site, of well-adjusted, ethical atheists, who clearly understand Life, the Universe, and Everything far more deeply than you do, obviously is deeply inconsistent with, and threatening to, your world-view, which is based on ancient fallacies such as the necessity of an external frame of reference, an ultimate reference point, for us to have any knowledge worth labeling as such, as having to be 100% 'provable' or else worthless.

Hence, rather than re-examine where you have gone off the rails in coming to your beliefs, you spend most of every post denying those plain facts of how functional atheists can be, in all aspects of human life, ethical, emotional, appreciation of art, and of the majesty and grandeur of the Universe revealed to us by the logically guided empirical study of Reality we label Science. And also denying your own inconsistency, of course.

Classic case of Denial.

And for anyone claiming to be 'consistent', making any reference to the Bible is ludicrous. It requires you to ignore massive chunks of it in a futile effort to make it 'consistent', inconsistently requiring some external reference point to decide which to delete.

The one point I will give you, your God is somewhat more consistent with reality than the 'loving' God/Jesus of conventional Christianity, but then you get wildly inconsistent again by claiming Atheists cannot know Love. Whereas by your own criteria, it is your belief which cannot render Love consistent with your God.

You really are a psychological mess, as you try to reconcile your world-view with just about every fact of modern secular societies.

 

Favorite oxymorons: Gospel Truth, Rational Supernaturalist, Business Ethics, Christian Morality

"Theology is now little more than a branch of human ignorance. Indeed, it is ignorance with wings." - Sam Harris

The path to Truth lies via careful study of reality, not the dreams of our fallible minds - me

From the sublime to the ridiculous: Science -> Philosophy -> Theology