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Cancer Immunotherapy: Hot With Promise, Potential Breakthroughs

If there's a science equivalent to the Oscars, or People magazine's Sexiest Man Alive, this might be it: last year Cancer Immunotherapy -- a technique that harnesses the body's own immune system to fight cancer — was named Science magazine's "breakthrough of the year."

In bestowing the honor, Science Editor-in-Chief Marcia McNutt, whose own father died of lung cancer, wrote: “We believe that 2013 marks a significant moment in cancer history, and today's achievements merit recognition and celebration, even if uncertainties remain.”

The idea of exploiting the body's own immune system to battle cancer isn't new. But what's getting all the buzz lately is some promising new data.

In December, 2013, researchers led by Dr. Carl June, director of translational medicine of the Abramson Cancer Center at the University of Pennsylvania, reported the results of a study testing immunotherapy on children with acute lymphoblastic leukemia (ALL). Of the 22 patients treated, 86 percent experienced complete remissions. And new research out of Memorial Sloan-Kettering Cancer Center this week shows that the treatment also had an effect on 14 out of 16 adult patients with ALL.

(A bit about how it works: This type of treatment, known as T-cell immunotherapy, functions a little like a blood transfusion. After a patient gives blood, scientists isolate T-cells, a white blood cell that is part of the immune system. They genetically alter these cells in a laboratory — programming them to kill cancer cells — before they are reinfused into the patient. Dr. June calls these modified cells “serial killer” T-cells.)

Despite the excitement, it’s still too early to tell what the long-term effect of this type of therapy might be, or why it doesn’t work in some of the patients who were treated.

To find out more, I spoke with Dr. June, whose worked was featured at the annual American Association for the Advancement of Science meeting in Chicago last week.

AM: Could you explain the concept of immunotherapy?

CJ: Immunotherapy is an approach that can be used for a number of diseases, from things like asthma and hay fever to cancer. In the case of cancer, where my laboratory has worked, there are a number of approaches to harness the immune system so that it can attack the cancer cells. In animal models, one can show that it can cure animals that have very advanced cancers.

Immunotherapy takes advantage of a major process and principle within the immune system, which is that once the immune system has been activated it makes memory. We all know this from childhood infections where once someone has a vaccine, they can then have lifelong protection. One of the very attractive aspects of immune therapy for cancer is that in principle it could last for the lifetime and not have short-term responses.

What is the difference between immunotherapy and a treatment such as chemotherapy?

Cancer was initially treated by surgery, and that began in the 1800s with anesthetics. Next was radiation therapy, and that’s still used today in various forms of cancer therapy. Chemotherapy then began to be used in the 1950s. And chemotherapy has been called cytotoxic treatment because it can use various mechanisms to directly kill cells. So the first cures of tumors by chemotherapy happened in leukemia. It used to be that all leukemia was rapidly fatal. By combining several chemotherapy drugs, investigators in the late 1950s and early 1960s were able to cure, for the first time, some forms of leukemia.

The problem with chemotherapy has been that for most cancers it’s not curative and it does have side effects. It will also kill normal cells — often those that are dividing. That’s why the major effects of chemotherapy are on cells that are rapidly dividing, which happens to be hair, so hair usually comes out with chemotherapy. Often times the immune system is damaged and so people get infections and bleeding — these can be side effects from chemotherapy.

It turns out that immunotherapy doesn’t have those properties. If it’s done appropriately it can target specifically the tumor cells and not have those kinds of side effects that chemotherapy does.

So what does this mean for a patient with a cancer today, for example a patient who has leukemia?

Until recently most forms of leukemia had not been cured. There had been therapies that delay it but there have not been curative therapies. And in many kinds of leukemia, seven or eight different kinds of drugs are used to treat the leukemia, but eventually the leukemia begins to become resistant to the therapies. The only therapy that has worked in that setting then has been a bone marrow transplantation. That usually involves using someone else’s immune system, maybe a brother or sister or an unrelated donor, and very high amounts of chemotherapy and radiation therapy.

Those bone marrow transplants can save many people who would otherwise die. But there are many complications to bone marrow transplants, and in general it’s only done in younger people. Older people with leukemia aren’t eligible for that.

So the new forms of immunotherapy now will hopefully, in the long run, do two things: replace the need to have bone marrow transplants, and benefit more people since it won’t have the limitations of bone marrow transplants where you have to find a donor who is matched to a patient.

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