Immunotherapy actually dates back almost 20 years, when a drug called interferon was used to non-selectively stimulate your body's immune system. And by non-selectively, I mean your body's immune system was augmented or stimulated to try to fight the cancer. But in addition, it had other side effects, and so while the concept was a good one, the execution of it in terms of effectiveness and side effects was not so good.
It was discovered about 10 years ago now that many cancers have proteins on their surface that act like camouflage to the body's immune system. And by that, I mean the body's immune system is supposed to detect things that are foreign and not supposed to be there, cancer being one of them. These proteins on the cancer cell surface camouflage the cancer cells from the body's immune system, so the cancer grows unabated. What the immunotherapies do is basically strip away the camouflage and allow your body's immune system to then attack the cancer that shouldn't be there.
[In recent years] two things happened. One was the discovery of these proteins on the surface, and the second was the design of antibodies or molecules to remove these proteins or the effect of these proteins from the cancer surface. So, it was a two-step process that occurred relatively rapidly. Since the development of the first immunotherapy drug, there have been six others that have come in rapid succession.
Immunotherapies, like many traditional chemotherapies, are given in the vein, so it's not an oral drug or it's not a shot. They're given either every other week or every third week. Each treatment is relatively brief. It takes about an hour and it's very, very rare that patients have any immediate side effects.
One of the concepts of having your body's immune system fight the tumor is that it takes a while for that immune response to develop. Typically, it will take anywhere from two to four months to develop. While that immune response is being developed, patients continue on the therapy. And then typically they continue on the therapy anywhere from a year to an indefinite period of time, with the average being about two years.
Depending on the condition that we're treating and whether it's an early stage cancer or a more advanced cancer, immunotherapy can be used by itself. More traditionally, it's used in combination with chemotherapy or radiation. Both chemotherapy and radiation, it's been discovered, augment or enhance the effects of the immunotherapy.
Typically, we assess the benefit of a therapy in a cancer patient in one of two ways. Sometimes a specific patient will have something that you can see externally, for example, an enlarged lymph node or mass in the neck. More commonly though, we do scans, either a CAT scan or an MRI or a PET scan, before the treatment. Then we do some treatment and then we do a follow-up scan. And this follow-up scan is compared to the prior scan and we look and say: "Okay, things that we saw before, are they the same? Are they smaller? Are there new spots? Are there no new spots?" Depending on what we see on the follow-up scans, which are done on a periodic basis, we determine whether the patient is benefiting or not.
The unique thing about immunotherapies is that a relatively brief amount of therapy, say a year or even two years, can last many, many years. So, think about the polio vaccine that you got when you were growing up. It's effect remains throughout the lifetime. The current round of immunotherapies may not have a lifetime benefit, but they certainly have a prolonged benefit, as opposed to chemotherapy, where the benefit that you get at the end of a course of chemotherapy is all that you're going to get.
With early stage lung cancer, for example, the goal is to cure or eradicate the cancer. In patients with more advanced cancers, previously the goals were much more modest, trying to modestly extend survival. These days, our goal is to turn what previously had been a rapidly fatal condition into a more chronic disease, not unlike diabetes or high blood pressure or high cholesterol. All those conditions, diabetes, high blood pressure or high cholesterol, are usually things that we can't eradicate in somebody, but we can control and allow them to lead a more or less normal life.
Immunotherapy really has worked in almost every cancer that it's been tried in with two notable exceptions. One is breast cancer and the second is prostate cancer. Both of those cancers, breast cancer and prostate cancer are cancers that are activated by hormones, estrogen in breast cancer, testosterone in prostate cancer. And even in breast cancer now, there are some inroads being made with immunotherapy. But pretty much every other cancer that it's been tried in, there's been either a small, or in some cases a really large improvement in survival in patients with advanced disease.
Immunotherapy shines in patients with recurrent cancer. Typically, the tumor has been exposed on the initial treatment that was designed to eradicate the cancer to some form of treatment, but then when it comes back, it has resistance to certain types of treatment, typically chemotherapy. For immunotherapy, that resistance doesn't show, so it's an ideal treatment for patients with recurrent cancer. But again, like everything in life, the devil's in the details, and you have to really understand the specifics of your particular type of cancer and the optimal treatment. It might not be immunotherapy by itself, but it might be immunotherapy in conjunction with something else like chemotherapy or radiation.
Increasingly we're finding that, for patients to get the most durable, the longest lasting benefit, immunotherapy needs to be combined with something else. [Immunotherapy] often allows us to reduce the dosage of the chemotherapy that we would use otherwise, or shorten the number of radiation treatments that would be required. So, the net effect is the side effects are more favorable, less toxic to patients in general.
Monoclonal antibodies are really targeted to a specific antigen or a protein on a cancer cell. Often times these antibodies have attached to them a compound that's toxic to the cancer cell, so instead of having this toxic compound go throughout the body, it's brought directly to the cancer cell.
You can think of an antibody like a key to a lock that fits into a specific part of the cancer cell and delivers that, so that's more of a targeted therapy than a specific immunotherapy. The immunotherapies that we've been talking about largely are therapies that strip the proteins on cancer cells and allow the body's immune system to more globally attack the cancer wherever it is.
Vaccine-based immunotherapies have been developed for certain types of lymphoma, which are tumors of the lymph glands. It's been tried in prostate and lung cancer with modest results. It's right now best described as a work in progress.
Immunotherapy for most patients, for many patients, is really like taking water in the vein. It's virtually devoid of side effects. The most common side effect is fatigue, which is mild. It's not a fatigue that inhibits your normal daily activities, but it is noticeable in many patients. Other less common side effects are effects on the GI tract, so people can have diarrhea; that's pretty uncommon. Skin rash, that's also uncommon, and then there are specific organs that are affected, like the thyroid. So, when we have a patient on immunotherapy, we're not only asking patients how they're doing and how they're feeling and examining them for skin rashes for example, we're also testing in their blood, their thyroid function, liver function and kidney function, looking for these less common side effects.
If you get these side effects, they can be prolonged. Typically though, if you take a break or stop the immunotherapy, those side effects resolve within a week to a month or two.
You need to know a couple things. You need to know: Is the tumor early or advanced? If it's early, there are probably curative strategies like surgery or radiation therapy to completely eradicate the tumor, and immunotherapy would not be appropriate for you.
If the tumor is more advanced, then there are some tests that can be done on the tumor itself looking for these camouflage proteins. One of the common ones is a protein called PD-L1, and to the degree that the tumor has a lot of this PD-L1 on the surface, that will predict that immunotherapy will be more likely to work.
With certain types of cancers, and again lung cancer's an excellent example, we would combine immunotherapy with chemotherapy. So, it's the type of cancer you have, whether it's early or more advanced, and then the characteristics of your specific tumor in terms of this protein expression that have to be taken into account.