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Our News - In Their Own Words - Rosenberg Interview

Training T Cells to Attack Cancer

NOTE:  This interview is an excerpt from NIH Radio Podcast, Episode 15.

Bill Schmalfeldt:
In the battle against cancer you hear a lot about treatments such as chemotherapy and radiation therapy, and one thing you're going to be hearing a lot more about is research into ways to coax a cancer patient's own body to fight off the invading cancer.  At the forefront of that kind of research is my guest today, Dr. Steven A. Rosenberg, of the National Cancer Institute.  Thanks for being with us, Dr. Rosenberg, on NIH Research Radio.

Dr. Steven A. Rosenberg:
My pleasure.

Bill Schmalfeldt:
Now I understand your goal in this research is to optimize each patient's immune response to attack and kill cancer cells.  Can you tell us how you're going about this; give us a little insight into what's being called adoptive cell transfer therapy against melanoma and kidney cancer?

Dr. Steven A. Rosenberg:
We've been trying to develop methods for treating cancer that take advantage of the body's own natural immune system.  So it's important to keep this in perspective.  We have today, three effective ways to treat cancer; surgery, radiation therapy, and chemotherapy.  And those treatments, properly applied, will cure about one half of all people who develop cancer in the year 2006. 

The problem is that the incidence of invasive cancer is so high that last year the 50% that could not be cured accounted for about 600,000 deaths in America alone.  One in every three Americans will develop an invasive cancer unless we find better ways to treat it.  One in every six will die of the disease.  So we've been looking at a different kind of treatment; not surgery, radiation or chemotherapy, which use an external force to treat the disease -- a scalpel, radiation beam or a drug.  Rather, we are trying to stimulate the body's own natural immune system to fight the disease.  And what we've done are two major things; we've developed a, an approach to identify, within the cancer patient themselves, immune cells, lymphocytes that are naturally present, but very weak and unable to cause a cancer, to a regression.  We take those cells out of the body.  We identify the strongest ones, grow them up to large numbers and then return them to the patient, along with IL2, which is required to keep them alive.

Bill Schmalfeldt:
To a layman, this almost sounds like science fiction.

Dr. Steven A. Rosenberg:
It's something that could be done readily in patients with malignant melanoma. This is a kind of cancer that starts in black moles in the skin, because those patients naturally have immune cells that you can isolate from within the tumor, we call them tumor infiltrating lymphocytes; grow them to large amounts, give them back.  And when we can do that, about half of all patients that we treat will undergo an objective regression of their cancer.  Now the problem is you can only do this in patients with melanoma, because you can't identify those cells in patients with other kinds of cancers.  And so what we're --

Bill Schmalfeldt:
And why is that?  Is it because melanoma is more easily visible?

Dr. Steven A. Rosenberg:
There's something unique about melanoma that enables the body to generate immune cells.  It has certain kinds of molecules on it that most cancers do not, do not have.  And so what about all of the other 95 percent of patients that develop cancer that's not melanoma?  Well, last week in the journal Science, we reported on a new approach that combines gene therapy with immunotherapy.  And what we describe for the first time is the ability to take a normal lymphocyte, a normal immune cell from a patient.  We just do a blood draw, much as you might withdraw blood for a laboratory test.  And we can now genetically modify that normal lymphocyte and put into it what we call receptors that now enable that normal lymphocyte to recognize a cancer, and so basically we take a normal cell and by genetic engineering, modify it so that it can go from being normal, unable to recognize a cancer, into a cell that can recognize the cancer. 

And we reported in Science last week that, in fact, we can now do this and generate cells that could recognize, not only melanoma, but to recognize about a half of all common cancers, like breast cancer, lung, colon, and so on.  So we can generate these cells in a laboratory that recognize common cancers, these genetically engineered cells.  When we return them to patients with melanoma, we saw two patients out of the 17 that we treated that had a regression of their cancer now on going beyond the year and a half.  And so it represents the first time that a gene therapy has been capable of successfully treating cancer. 

Now we haven't treated patients with other diseases other than melanoma yet, with this approach.  We are waiting for approval from the Food and Drug Administration.  I'm hoping we’ll get it within the month.  So we'll be able to start these clinical trials, to treat patients with other kinds of cancers, but we have done that yet.

Bill Schmalfeldt:
With this success in the books now, where do you go from here?

Dr. Steven A. Rosenberg:
Well, there were only two patients that responded.  We have much better receptors.  We think we can do this far more effectively.  After all, the report that we published last week is a year and a half to two years old.  We had to wait to see if the patients whose cancers went away, the cancers stayed away, and they have.  So we published it, but we now can do it, I think, much more effectively with much more powerful receptors.  We can get the genes into the cells; do the genetic engineering more efficiently.  There's a lot of work to be done.  In fact, we're working around the clock to try to improve the treatment.

Bill Schmalfeldt:
Speaking of that working around the clock, what can you tell us about the research environment here at the National Institutes of Health?  How the environment at the National Cancer Institute, the Center for Cancer Research, how does it facilitate progress with the whole bench to bedside research?

Dr. Steven A. Rosenberg:
Well, the NIH is quite unique in its intramural research.  We have a very vigorous, scientific research program and we have a hospital at the Clinical Center that is solely devoted to making progress.  The only patients that we see here are patients that cannot be successfully treated with today's medicine.  We are trying to create the medicine of tomorrow.  That's the only reason that this hospital exists and that is to make progress. 

The intramural program here at the NIH represents a marriage of science and clinical work, unlike that in any other institution in the world.  We have side-by-side our research laboratories, as well as the wards in which we treat patients and we carry reagents that we develop in one to the other for treatment.  And so the NIH is a unique institution that marries basic research and clinical research in a way that is quite remarkable.

Bill Schmalfeldt:
Why is it important to closely coordinate the roles of the pathologist, the surgeon, and the nurses to get the kind of results you are seeing in your research?

Dr. Steven A. Rosenberg:
Well, we exist here at the intramural program of the NIH for only one reason, and that is to make progress.  The patient has a problem, a medical problem, that can be treated successfully by modern medicine, then they will receive those treatments and we will not see those patients here.  We’re only here to attempt to develop treatments for patients that cannot be successfully treated today.  And that requires a team.  It requires a team of scientists, of physicians, of pathologists, of clinical laboratory personnel and all of that exists right here in the Clinical Center, all designed to try to make progress.

Bill Schmalfeldt:
It all sounds very exciting.  Anything else you want to add?

Dr. Steven A. Rosenberg:
I just emphasize that, before we can bring any treatment to patients as we reported last week, it requires a combination of basic scientific research, as well as clinical work that is equally -- that are equally important.  It's incredibly important that we support basic research so that the tools can be available to translate to patients.

Bill Schmalfeldt:
Dr. Steven A. Rosenberg of the National Cancer Institute -- again, thanks for spending some time with us.  You've told us a lot, and I think it'll probably raise questions in the minds of folks who are listening to us today.  We'll recommend that they log on to www.cancer.gov to get all the information, and what the current events are here at the National Cancer Institute.  Thanks again so much for spending some time with us today on NIH Research Radio.

Dr. Steven A. Rosenberg:
You're welcome.

[end of transcript]

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