By Richard Frank, MD
Ever since the late 1800′s, when Dr. William Coley tried to treat cancerous tumors in his patients by injecting those tumors with live bacteria (“Coley’s toxins”) to elicit an immune response, scientists have been trying to harness a patient’s own immune system to fight their cancer. They have tried every manner possible, including vaccination with modified tumor cells or mixtures of tumor proteins, high doses of immune-stimulating chemicals such as interferon and interleukin, the removal/modificiation/return of a patient’s immune cells, and the development of drugs to redirect the immune system against cancer. After 120 years of research, thousands of careers, and billions of dollars spent on this effort, the result was by and large a resounding failure. That is, until now.
I do not mean to imply that we have not had any effective cancer therapies that use a patient’s immune system. Since the late 1990′s, antibody therapies such as Rituxan for B-cell non-Hodgkin’s lymphoma and Herceptin for Her2 positive breast cancer have radically transformed the outcomes for patients with these diseases. But although these antibodies are types of immune molecules (our immune system normally makes antibodies to fight infections) they work mainly by directly attacking cancer cells. Indeed, improvements on this killing potential were showcased at the recent American Society of Clinical Oncology (ASCO) meeting in Chicago, when the drug T-DM1, which is Herceptin linked to a chemotherapy drug, was shown to fight breast cancer when the traditional Herceptin drug could no longer do so. Still, this is not relying on a patient’s immune system to destroy cancer cells.
The breakthrough in immune therapy to fight cancer started with the drug ipilumumab (YERVOY), which was approved by the US FDA in 2011 for the treatment of metastatic melanoma. Clinical trials showed that Yervoy significantly extended the lives of melanoma patients and was the first major advance in this disease in many decades. The next breakthrough was introduced at this year’s ASCO meeting, when it was shown that the drug “anti-PD-1″ led to the sustained shrinkage of cancerous tumors in patients with advanced non-small cell lung cancer, melanoma, and kidney cancer who had already “failed” standard therapies (this medicine is still undergoing clinical testing and is not yet available for general use).
What are these new drugs and why do they represent breakthroughs in the treatment of cancer? Ipilumumab is an antibody that blocks the function of a molecule called CTLA-4. Anti-PD-1 is another antibody therapy, which blocks the function of PD-1. Both CTLA-4 and PD-1 are present on the surfaces of our immune T-cells. Both molecules normally function to block the over-stimulation of our immune system against infections or against ourselves, preventing damage to the body and the development of autoimmune diseases, such as Lupus and Rheumatoid Arthritis. But they also block the T-cells of cancer patients from directly attacking their cancers. So, by releasing the brakes on the immune system, rather than “stimulating” the immune system as so many have tried to do, these new types of medicines are, for the first time, truly unleashing the potential of our immune systems to fight cancer. This new approach to fighting cancer stands to revolutionize how the disease is treated.