How Does Cancer Immunotherapy Work?

In August of 2015 ninety-one year-old former US President Jimmy Carter began to exhibit brain cancer symptoms. Tests soon revealed that melanoma he had had treated several years earlier had spread to his liver and his brain. The former President was sure he only had a few months to live, but his doctors were able to refer him for a relatively new form of treatment called immunotherapy. To the former president's considerable surprise, the treatment worked, and in December of the same year he was able to announce that his cancer was "gone." In the year since, has has remained active and vigorous even as he continues to receive his treatment.

Cancer immunotherapy for melanoma and for other forms of cancer is a therapy that is not only available for former presidents. Tens of thousands of people have gone into remission from cancers that 10 years ago would have been considered a death sentence. Cancer immunotherapy isn't always successful. For melanoma, for example, only about 30 percent of patients go into remission as did President Carter. Another 30 to 40 percent have partial remission. Success rates for other kinds of cancer are lower, maybe 20 to 40 percent.There is no reasonable expectation that anyone who receives the therapy will simply live forever. But this new method of cancer treatment holds out  hope for millions of people who are holding on through the arduous experience of cancer and cancer treatment.

Cancer immunotherapy is the biggest advance in the war on cancer so far in the twenty-first century. Advances in immunotherapy have attracted investments of tens of billions of dollars. They have spurred hundreds of clinical trials. If you get cancer, there's a chance immunotherapy will be available for you. Here are answers to some basic questions about immunotherapy for cancer. 

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What Is Cancer Immunotherapy?

Immunotherapy is a technique of treatment that relies on stimulating the immune system to fight disease. It helps the body work harder and smarter against cancer cells. One of the reasons the immune system has trouble defeating cancer is that tumors consist of our own cells. The immune system cannot recognize them as foreign to the body, the way it can recognize a bacterium or a parasite or a virus. Unlike radiation or chemotherapy, which are designed to kill cancer cells, cancer immunotherapy enhances the natural abilities of the body to fight disease.

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Are There Different Kinds of Cancer Immunotherapy?

One form of cancer immunotherapy keeps cancer from hijacking parts of the immune system. When the immune system is fighting infection, certain proteins keep it from destroying healthy cells along with germs and infected tissue. Cancer can also produce these proteins so the immune system doesn't attack it. These proteins act something like hitting the brakes of a car to keep the immune system. These new drugs, known as checkpoint inhibitors (so called because they allow the immune system to pass certain "checkpoints" to proceed to attack infection) "release the brakes" so the immune system can attack cancer the same way it attacks germs. This was the kind of immunotherapy given to President Carter. 

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There are currently four checkpoint inhibitors that are approved for use in treating cancer in the United States and many other countries. The drugs are Keytruda (pembrolizumab), by Merck, Yervoy (ipilimumab) and Opdivo (nivolumab), made by Bristol-Myers Squibb, and Tecentriq (atezolizumab), by Genentech. In the United States, not every kind of immunotherapy is covered by insurance, but these four drugs are. Opdivo is even heavily advertised on TV. Checkpoint inhibitors are approved for treatment of melanoma, Hodgkin's lymphoma, and cancers of the bladder, lungs, kidneys, and head and neck. They are being tested for many other forms of cancer.

What About Cell Therapy?

Checkpoint inhibitors have an action analogous to taking your foot off the brakes of your car, while cell therapy acts something like pressing down on the accelerator. In cell therapy, some of the patients white blood cells are removed and then genetically modified. They are cultured so more white blood cells can be returned than were withdrawn. Patients get IVs of their own genetically modified white blood cells like a transfusion. Each batch of cells has to be individually modified for the specific patient from their own cells.

Cell therapy is primarly used for leukemia and lymphoma, with 25 to 90 percent response rates. Some patients will stay well for years and years, but others will relapse in just a year.

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Bispecific Antibodies

Bispecific antibodies are genetically engineered so that they "stick" to both a T-cell (white blood cell) circulating in the bloodstream and a cancer cell. The antibody "glues" a white blood cell to cancer so the cancer is destroyed. In the United States, there is one drug in this class approved for fighting a rare form of leukemia. The drug is called Blincyto.

Vaccines Are Part of Cancer Immunotherapy, Too

Certain vaccines are used for treating specific cancers. Unlike vaccines used to prevent infections, vaccines for cancer are given after cancer has been diagnosed to stimulate the immune system. Vaccines for cancer are not widely accepted. The only vaccine approved in the United States for treating cancer is Provenge, used for treating prostate cancer. It is successful in only a minority of cases, and extends life for months, not years. In some other countries the BCG vaccine, which is primarily used to prevent tuberculosis, is used to treat bladder cancer. It stimulates the immune system in specific ways that enable it to attack this cancer, but not other forms of cancer.

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Are There Side Effects from Cancer Immunotherapy?

Checkpoint inhibitors can cause the immune system to act a little too well. The immune system does its job by generating inflammation. These drugs can cause breathing problems and diarrhea. They can trigger inflammation that causes joint and muscle pain or even rheumatoid arthritis. Taking two checkpoint inhibitors at the same time to fight cancer can sometimes cause severe damage to the heart, or damage the thyroid and/or pituitary gland. These effects can be minimized with the use of steroid drugs like Prednisone, but steroid drugs cause their own side effects.

Cell therapy can cause potentially fatal overstimulation of the immune system that has to be treated in the ICU.

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How Much Does Cancer Immunotherapy Cost?

The cost of checkpoint inhibitors is usually around $150,000 a year, although insurance will usually cover it (although Medicaid sometimes will not). Cell therapy, when it is approved, will cost $300,000 to $500,000 a year in the United States, but will also be covered by insurance. Other forms of cancer immunotherapy may cost $90,000 a year and up.

Any oncologist will be able to explain and if appropriate prescribe cancer immunotherapy. Oncologist offices will usually work with their patients to make sure they stay on the right insurance plans to get their treatment covered. If you can't afford treatment, you may be able to get free drugs by participating in a clinical trial. Links to two sources of information about clinical trials are posted at the end of this article. However, if you participate in a clinical trial, you may get either the investigational drug or a placebo. You will not know which, and neither will your doctor.