Putting The Immune System To Work Against Cancer
Researchers have evidence that the immune system can fight cancer—they have been heavily investing in the search for a drug that will boost our own body’s ability to combat cancer. Some immunotherapy approaches rely on stimulating the immune system throughout the body, while others require a patient’s immune cells to be removed and genetically engineered to attack specific cancer cells. But while many of these approaches were successful, each still carry negative effects—they were either time-consuming or triggered serious autoimmune side-effects.
But now, researchers at Stanford University may have discovered a treatment that’s not only quick, but also doesn’t send the body’s immune system into overdrive. In a recent study in the journal Science Translational Medicine, Dr. Ron Levy and his team found that when a small amount of two immune stimulating compounds was injected directly into mouse tumors, they disappeared in less than 10 days. In less than 20 days, tumors that had not been injected with the compounds also vanished. Levy joins Ira to discuss how this immunotherapy treatment avoids the pitfalls of its predecessors, and his hopes for its success in clinical trials that are now underway.
Ronald Levy is a professor of Medicine and director of the Lymphoma Program at Stanford University in Stanford, California.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. It’s pretty clear by now that the immune system can fight cancer, and researchers are heavily invested in the search for a way to boost the body’s own cancer fighting properties. Some of the immunotherapy approaches, when they’ve been tested, they have met with some amount of success, but they also have their downsides.
They’re time consuming, or they trigger serious autoimmune side effects. But now researchers at Stanford have discovered a treatment that’s not only quick, but also doesn’t send the body’s immune system into overdrive, at least in laboratory tests in mice. Dr. Ron Levy is Professor of Medicine and Director of the lymphoma program at Stanford University. Dr. Levy, welcome to Science Friday.
DR. RON LEVY: Thank you for having me on the program. I always enjoy your program, Ira.
IRA FLATOW: Thank you. You’re welcome. So tell us about what does this treatment do to tumors in mice? What are you giving them and how does how do the tumors react?
DR. RON LEVY: Yes. Well as you just said, we’re now coming to appreciate the immune system can fight cancer. It generally is appreciated it can fight the invaders from the outside. The bacteria and viruses that cause illness, but now we know that it can fight cancer, the invader from the inside of the body.
So what we’ve done is to engineer a way to get the immune system revved up, just against the cancer, and not against the rest of the body. We’ve injected stimulants in the immune system directly into the tumor itself in one place in the body, and those immune cells that are there trying to do their job are now woken up, and stimulated, and fight the cancer not only there, but they travel around and seek and destroy cancer all over the body.
IRA FLATOW: Wow. So they go into the bloodstream and find the same cancer that you’re treating, or all cancers that might be there?
DR. RON LEVY: Well actually, they find the same cancer that we’re treating, and we’ve determined that by putting two different cancers into the body , and stimulate those cells. And they go and fight the same cancer, but not an unrelated cancers. So they’re very specific in what they’re recognizing about the cancer that we’ve triggered them against.
IRA FLATOW: And so this is only working for tumors, right? Not for leukemia or other kinds of cancers that are not solid tumors?
DR. RON LEVY: Well actually, we’ve used a number of different kinds of cancers in the mice, leukemias and lymphomas melanomas, breast cancer, and a variety of other kinds of cancer. So this is a strategy that could go for cancers across the board.
IRA FLATOW: Well, people are going to say, why can’t I have this tomorrow?
DR. RON LEVY: Yes. Well that’s a good question. As you know, mice are not people. And there have been a lot of things that have worked in mice that have not worked in people. So we’re proceeding slowly. We’re starting a clinical trial just in lymphoma patients, low grade lymphoma, the kind that grows slowly. It gives us time to make observations.
And also, lymphoma is the cancer of the immune system, so most of our mouse results are in that kind of cancer, the lymphoma. So we’re starting with patients with lymphoma and we’re going slowly at establishing that it’s safe first, and having established that, we’re looking for good effects to happen against their cancers.
IRA FLATOW: So what is it about your technique that works so much better than other techniques that have failed?
DR. RON LEVY: Yes. Well we screened, in the mouse experiments, we’ve screened many different candidate immune stimulants, and many combinations of them. And we came up with a particular combination that works really well in the mice.
And this is two different drugs, one that triggers the macrophages, the engulfing cells in and around the cancers, and then another one that triggers the t-cells, the cells that can remember what they’re supposed to target. And these two drugs work very well together. In fact, they’re even synergistic even better than any additive effects of the two. And they work really well, and so far that’s the best combination we found.
IRA FLATOW: What would you use this most, let’s say, if it did work in people, would it be something for post-surgery? Or could you just give it as the terms of the primary treatment?
DR. RON LEVY: That’s a really good question. We need a place to inject, and so we need to know where the cancer is in the body or be able to reach it with a needle so we can inject our stimulants there.
But it could be for a situation where the cancer has come back and we know where it is, or it could even be situation before the tumor is removed from the body, where we know where we’re going to remove it from, and we know where that place is. So it could be administered right then and there before the primary surgery, so-called neoadjuvant therapy.
IRA FLATOW: So the reason the autoimmune reaction does not kick in here and the body attacks itself, as in so many other cases, is because you have just, basically by trial and error or design, figured out the right combination.
DR. RON LEVY: We figured out a good combination, but we’re also using very low amounts of these stimulants. So low that they don’t stimulate generally throughout the body, just in the place we inject them. And so by using very low amounts, and particular combination, we think we can avoid this the autoimmune problems that have happened from generally taking the brakes off the immune systems throughout the body.
IRA FLATOW: So once you wake up the immune system, it goes ahead and basically it does its thing.
DR. RON LEVY: Yes. The immune cells travel throughout the body, and go everywhere actually, even into the brain. And we’ve even been able to eliminate the tumor when it’s in the brain. One of the really important parts of our study, since the mice that we usually work on get their tumors artificially, we inject those tumors and let them grow and then treat them.
A lot of work has been done in that way. We were able to actually treat a naturally arising tumor, a breast cancer, that happens because a certain strain of mice has a gene which makes them get breast cancer. All the mice in this strain get breast cancer in all their mammary glands. They have 10 different mammary glands and they all come down with cancer.
So Idit Sagiv-Barfi, the scientist working on this project, was able to perform our vaccination with these stimulants on the very first cancer that arises in these mice, and by triggering that immune response, she was able to prevent all the other cancers that occur throughout the body in all the other mammary glands.
IRA FLATOW: Wow. That sounds too good to be true.
DR. RON LEVY: It might be too good to be true. We’ll not know until we try it in people, and we have to go slowly, and first establish that it’s safe.
IRA FLATOW: Wow.
DR. RON LEVY: I want to emphasize once again that this first foray into people is just for lymphoma, patients with lymphoma and the slow growing kind called low grade lymphoma.
IRA FLATOW: Well, this is quite interesting. I want to thank you, Dr. Levy for taking time to be with us. And would you keep in touch?
DR. RON LEVY: Thank you very much.
IRA FLATOW: Let us know how this is progressing as you go ahead.
DR. RON LEVY: OK. Thank you very much for having me.
IRA FLATOW: You’re welcome. Ron Levy. professor of Medicine and Director of the Lymphoma Program at Stanford University.