Keeping Cancer in "Check"

When bacteria or a virus invades the body, the immune system acts as the first line of defense. This is a natural reaction for the immune system, which is designed to help keep you healthy.

Dating to the 1800s, scientists believed they could use bacteria to purposely infect someone with a disease in hopes of curing them of cancer. These ideas are the earliest forms of immunotherapy, which uses substances to stimulate or suppress the immune system to help the body fight cancer cells. This therapy has become a major player in the treatment of different types of cancer today.

The initial tools for immunotherapy were crude — vaccines made of bacterial products and, later, from tumor cells — and mostly ineffective, with rare responses. Newer types of immunotherapy, such as cytokines and monoclonal antibodies, are proving to extend patients’ lives and limit side effects.

We have long known that the immune system tries, often in vain, to reject cancer cells just like it does bacteria and viruses. For example, patients with melanoma mount an immune reaction against melanin, the skin pigment that is often overexpressed in melanoma — the reason melanoma lesions are usually dark. Therefore, patients get vitiligo, or light spots indicative of this reaction, and develop autoantibodies against the thyroid gland. These gland’s cells have similarities to melanoma cells and can keep the body from making hormones it needs to work correctly.

Over time, the immune system “fatigues” and can no longer fight off tumor cells. It took a long time to understand how this happens. However, a big breakthrough occurred with the discovery of “checkpoints,” starting with CTLA-4 — its real function is to prevent immune system overactivity, which can cause tissue damage. However, cancer cells can co-opt checkpoints to stop the immune system from attacking them. This led to the development of the first checkpoint inhibitor, Yervoy (ipilimumab), an antibody that targets CTLA-4. It was ultimately approved for advanced melanoma after a landmark trial showed that it improved the dismal survival rates for that disease. The checkpoint system was discovered by Drs. James Allison and Tasuku Honjo, who shared last year’s Nobel Prize in physiology or medicine and are considered the pioneers of immunotherapy. Since the 2011 Food and Drug Administration approval of Yervoy, six more checkpoint inhibitors have been approved.

Although there is much to learn about the intricacies of how the immune system interacts with cancer, advances are occurring rapidly as immunotherapy for cancer has exploded with myriad ongoing clinical trials and newer drugs coming on line constantly. Many new scientists and clinical investigators — and an incredible amount of money — are invested in developing immunotherapies, both new and old, to help fight cancer of all kinds.