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Immunotherapy is a treatment approach that harnesses the power of our own immune system to fight cancer. Excitement is growing about new drugs that unleash the immune system to destroy cancer cells. In fact, just this past year, the US Food and Drug Administration (FDA) approved new immunotherapies for the treatment of melanoma, lung cancer, bladder cancer, lymphoma and kidney cancer.

Although cancer immunotherapy has only recently attracted widespread attention, its origins go back more than a century. In the 1890s, William Coley, a surgeon at New York Cancer Hospital (the predecessor to Memorial Sloan Kettering Cancer Center in New York) discovered that cancer patients who suffered from infections after surgery sometimes saw their cancers regress. His finding led to the development of Coley's toxins, a cocktail of inactive bacteria injected into tumors that occasionally resulted in complete remission. But eventually the use of this treatment fell out of favor.

In the 1960s and 1970s, research by Memorial Sloan Kettering investigator Lloyd Old led to the discovery of molecular markers (called antigens) on the surface of cancer cells, which enabled the development of the first cancer vaccines and led to the understanding of how certain white blood cells – immune cells known as T cells or T lymphocytes – can be trained to recognize cancer.

T cells

White blood cells called T cells (green) are vital in the immune system's response to infections and cancer. Innovative treatments pioneered by Memorial Sloan Kettering researchers harness the cells' ability to recognize and destroy cancer cells.

Scientific Breakthroughs Pave the Way for Immunotherapy

In recent years, a number of scientific breakthroughs have helped breathe life into the idea that a person's immune system is inherently capable of responding to cancer and can be summoned to effectively defend the body against it. In fact, clinical trials conducted at Memorial Sloan Kettering and elsewhere have shown remarkable successes for new cancer immunotherapies.

One of the pivotal milestones in immunotherapy research is the work of immunologist James Allison, who showed that a molecule called CTLA-4 – a protein receptor on the surface of T cells – acts as a brake on T cells, preventing them from carrying out immune attacks. He later developed an antibody that blocks CTLA-4 and showed that "releasing" that brake allows T cells to destroy cancer in mice.

Anti-CTLA-4 eventually became ipilimumab (Yervoy®), a drug approved in 2011 for the treatment of metastatic melanoma, the most deadly form of skin cancer. Dr. Allison, together with Memorial Sloan Kettering physician-scientist Jedd Wolchok, helped guide the development of ipilimumab from the first laboratory studies through the late-stage clinical trials that led to the drug's approval.

Jedd Wolchok

Jedd Wolchok, MD, PhD, Chief of the Melanoma & Immunotherapeutics Service at Memorial Sloan Kettering, has played a central role in developing and testing the immunotherapy drugs known as checkpoint inhibitors.

Helping Patients Today

Great promise is being shown by this approach, known as immune checkpoint blockade therapy. Memorial Sloan Kettering has played a leading role in developing and testing these promising immunotherapies, which, in addition to ipilimumab, include nivolumab (Opdivo®), pembrolizumab (Keytruda®) and atezolizumab (Tecentriq®). The therapies have produced remarkable results, controlling cancer completely in some patients with highly advanced melanoma, as well as in patients with lung, kidney, lymphoma, and bladder cancers.

One study led by Dr. Wolchok in 2013 found that more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of ipilimumab and nivolumab, suggesting that these two drugs may work better together than on their own. This combination of immune drugs was approved by the FDA in 2015 for use in patients with metastatic melanoma. This is the first-ever combination immunotherapy to receive approval by the FDA.

Check out Joanne's Story to learn more about immunotherapy success stories.

Hope for the Future

The FDA approval of checkpoint blockade therapies — also known as checkpoint inhibitors — has dramatically improved therapeutic options for many patients, with many different types of cancer.

But the approach does not work for everyone. Research is underway to help make immunotherapy more widely effective and it's yielding important insights about how immunotherapy drugs work and how they could be improved.

For example, a number of clinical trials are now looking more closely at the effectiveness of combining immunotherapy drugs in order to boost the number of responders. In addition, investigators are working to better understand how treatment responses relate to the underlying biology of a tumor. Eventually, the goal is to use characteristics of the tumor to choose the right therapy for the right patient.

As laboratory research and clinical trials continue at Memorial Sloan Kettering and elsewhere, there will be new opportunities for more patients to benefit from immunotherapy — a promising approach that is transforming the way we think about cancer care.

Learn more about immunotherapy and cancer at mskcc.org/immunotherapy.

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