Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« A Chemical Biology Conference | Main | Stuart Schreiber at the Challenges in Chemical Biology Conference »

July 24, 2013

More Details on T-Cell Leukemia Therapy

Email This Entry

Posted by Derek

There's an excellent overview at Science of the work of David Porter and Carl June at the University of Pennsylvania on T-cell-based cancer therapy. It turns out that when the dramatic reports came out on their first three patients, the team was out of funding and trying to see if they could get someone interested. They did:

. . .Porter and June weighed their next step. They were itching to test the cell therapy in more people with leukemia, and to do that they needed money that they didn’t have. “We basically decided that we would just publish with three patients,” June says. Getting the word out, he hoped, could shift the dynamic in their favor. Porter was game to try, but skeptical that any reputable journal would accept a paper with an n of 3.

He turned out to be wrong. The New England Journal of Medicine welcomed a report about Olson and his mouse dose of T cells. Science Translational Medicine, Science’s sister journal, snapped up a manuscript detailing all three patients. The papers were published simultaneously on 10 August 2011. . .Porter was en route to vacation in western Maryland with his family when the embargo lifted. His phone started ringing. “I was in the car for 8 hours that day,” he says. “I spent 8 hours straight on my phone, answering e-mail, answering phone calls. It was a story that took us all by surprise. It kind of went viral.” June fielded 5000 requests from patients and their families for the therapy. Eight hundred media outlets worldwide covered the story.

And the funding reappeared, as well it might. Now the problem is turning this into something that can be used routinely, and that is nontrivial, as we technical types say. T-cell therapy is patient-specific. You don't just start treating everyone with injections out of the vials that you keep in the fridge - every patient is a new experiment, and the process starts from scratch. That means that many sources of error and variability that are ironed out with a traditional drug therapy are still going to be present, every time, for every person, and it also means that the cost is going to be high. But it may well be worth every bit of the trouble and expense.

The article gives a good look at how hard it is for a discovery like this to be born. The first person to try modifying T cells as an anticancer agent was probably Zelig Eshhar at the Weizmann Institute, back in the 1980s. Then a few other labs picked up the idea, notably Michel Sadelain at Sloan-Kettering, Steven Rosenberg at NCI, and Malcolm Brenner at Baylor, but technical difficulties slowed things down at every turn. Isolating the T cells reproducibly, inserting new genes into them, figuring out what genes to insert, getting everything successfully back into a patient - each of these steps took years of work and frustration.

Success came as everyone narrowed down on the CD19 protein on the surface of B cells. Those were attractive targets, because you can actually survive without them - which was a key hurdle, because once you unleash the T cells, they're probably going to kill off everything they're targeted for. It turns out that the CD19 marker is basically universal in B-cell leukemias, so this looked like the best targets on several grounds. There were actually four other trials (using very similar approaches) running at other centers when Porter and June got going.

But the combination of stimulatory signals and the choice of vector in the Penn trials set off the extraordinary clinical effects. There was no way to know this - in fact, some other approaches looked a bit more promising. But that's clinical research, and that's oncology, for sure.

Unfortunately, but predictably, there have been legal problems. St. Jude and Penn are involved in lawsuits about prior research agreements, and whether the current therapies are covered under them. I assume that this will be worked out, to the enrichment of a phalanx of lawyers, but it's unfortunate. It doesn't seem to be slowing anyone down much, though, which is the good news. Trials are underway all over the place on variations of this idea, and the Penn group is about as busy as they could possibly be:

Still, physicians like Porter and Grupp are mindful that this isn’t life-changing for every- one. “When I’m doing informed consent with these families, the first thing I say is, ‘Forget everything you’ve read about this,’ ” Grupp says. “Nothing could possibly be as promis- ing as the various articles about this make it seem.” Only four people, including Emily, have been followed for more than a year. A looming question is whether CAR therapy can work in solid tumors, and June and others are opening clinical trials to try and find out.

Nearly 3 years after the summer that changed everything, the Penn group is still working flat out to keep up: enrolling as many patients on the trials as they can, working with drug regulators to discuss how best to study the cells with an eye toward approval, collaborating with Novartis to train their employees and streamline the cell-generating process.

This all should be seen in a larger context of immunotherapy, too. People have been trying to recruit the immune system for years in the fight against tumor cells, with mixed success. But we may be just on the verge of knowing enough about what we're doing to get more of these to work. At this point, it would not surprise me if immune system approaches become the dominant form of treatment for several types of cancer over the next 25 years. The next few years will tell us.

Comments (7) + TrackBacks (0) | Category: Cancer | Clinical Trials


COMMENTS

1. metaphysician on July 24, 2013 4:18 PM writes...

So, this reminds me of a question I've had: Why is it that there is so much progress in treating some cancers, and so little progress in others? What seems to make certain cancers much easier to treat than others?

Permalink to Comment

2. Matilda on September 29, 2013 7:08 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

3. Matilda on September 29, 2013 7:08 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

4. Matilda on September 29, 2013 7:09 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

5. Matilda on September 29, 2013 7:10 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

6. Matilda on September 29, 2013 7:10 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

7. Matilda on September 29, 2013 7:10 PM writes...

Perhaps diseases like Leukemia are easier to treat because when one eradicates the source medicine is evolved enough to replace the healthy cells. It is also a "movable" cancer, meaning there is a constant regeneration of new cells. Those are significant reasons why the above mentioned treatment works. The difficulty in annihilating solid tumors is that unless you can remove a significant portion they cannot stop the expansion in an area already damaged and saturated by cancer cells. In the above T-cell treatment that targets protein, the problem they have going is that they lack either knowledge about what purpose the proteins serve in the body and/or lack a replacement treatment for the healthy cells.

This treatment isn't going to be as expansive as being suggested and a lot of people will sadly be hurt prior to realizing this. It's not a one trick pony, but it is limited if healthy cells contain the protein they need to target and they do not have a way to replace the cells before the person dies from complications. You'll see....

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
Gitcher SF5 Groups Right Here
Changing A Broken Science System
One and Done
The Latest Protein-Protein Compounds
Professor Fukuyama's Solvent Peaks
Novartis Gets Out of RNAi
Total Synthesis in Flow
Sweet Reason Lands On Its Face