The Fight is Within Us: Cancer Immunotherapy

By: Miriam Saffern  |  August 29, 2016
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Cancer_cells_(1)“You have cancer.” It’s the phrase that everyone fears. But is it true? Do we all have cancer? Our cells are remarkably efficient in producing molecules and signals that are necessary for them to carry out their functions and ensure that we are not overtaken by disease. However, as it is with even the most fine-tuned of machines, mistakes are made. Ordinary cells can transform into cancer cells and multiply unrestrained, forming malignant tumors which do not respond to body signals that induce the death of unneeded cells. Luckily, we possess our own Navy SEALs, the cells of the immune system, which scout out foreign substances in our bodies, typically bacteria and other outside invaders, and oust them from their place before they harm us. These cells can also kill cancerous ones in what is known as the elimination phase of immune surveillance. With this system, we are protected from cancer every day. What happens when the power of the cancer surpasses the force of our immune system? The equilibrium phase then ensues, where some cancer cells are being destroyed but others are mutating and thus surviving. When the escape phase begins, our bodies’ defenses are no longer able to detect the mutated cancer cells because they are not seen as foreign; the cells proliferate and begin to threaten our health. This is when the dreaded words in the oncologist’s office are uttered: “You have cancer.” Until recently, the three common treatments for cancer were surgery, chemotherapy, and radiation. Now that it is understood that the immune system has the ability to fight cancer, a fourth pillar of treatment, known as immunotherapy, is being heralded as a powerful new therapy with unparalleled potential. Cancer immunotherapy is based on the principle that our bodies have the tools to cure cancer; they simply need to be released or enhanced. One effective type of immunotherapy is called checkpoint blockade therapy. This therapy unlocks our immune toolbox by blocking molecules called checkpoint proteins. Checkpoint proteins prevent overstimulation of the immune system and are what scientists dub the “brakes” of the immune system. Cancer cells take advantage of these checkpoints to evade attack by the immune system. In 1996, Dr. James Allison discovered that a surface protein called CTLA-4, found on cytotoxic T lymphocytes, the primary killers of the immune system, is one such brake that cancer cells use to evade the wrath of T cells. He also showed that a specific antibody can bind to CTLA-4, essentially inhibiting the checkpoint and thereby allowing the T-cells to attack the cancer. With the help of Dr. Jedd Wolchok of Memorial Sloan Kettering Cancer Center, Dr. Allison developed the anti-CTLA-4 checkpoint inhibitor ipilimumab (Yervoy). The FDA approved the drug for treatment of late stage melanoma in 2011. Drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) target PD-1, another checkpoint. Dr. Wolchok also discovered that these drugs work better in tandem than they do alone; a regimen of ipilimumab and nivolumab for melanoma became FDA-approved in 2015. Another new and improving immunotherapy, called adoptive cell therapy (ACT), takes the tools of the immune system and sharpens them. In one kind of ACT, immune cells called tumor infiltrating lymphocytes, which possess the inherent ability to detect cancer, are extracted from the tumor and stimulated with immune molecules such as IL-2 that cause them to multiply. The cells are then returned to the patient’s bloodstream to kill all of the cancer cells. T cells can also be engineered with viral vectors to express protein receptors that bind surface molecules known to exist on certain types cancer cells. The most promising of the ACTs is CAR T cell therapy, pioneered by Dr. Michel Sadelain of Memorial Sloan Kettering, and Dr. Steven Rosenberg and Dr. Carl June of the University of Pennsylvania. A CAR T cell is a T cell engineered to express a protein called a chimeric antigen receptor – a cross between an antibody and a T cell receptor. It binds strongly like an antibody, and kills like a T cell. This therapy works best for blood cancers such as acute lymphoblastic leukemia (ALL). The CAR T cells are engineered to recognize the CD19 antigen present on B cells, whose excessive proliferation is the hallmark of ALL. In a recent New York Times series spotlighting cancer immunotherapy, Dr. Bruce Levine, director of cell production at the University of Pennsylvania commented, “We’re in the Model T version of the CAR now. What’s coming along are Google CARs and Tesla CARs.” Work by Dr. Alexander Rudensky of Memorial Sloan Kettering on regulatory T cells, which prevent overly intense immune responses, can also help with the improvement of immunotherapy. Though the noteworthy breakthroughs in cancer immunotherapy research have only begun to take shape in recent years, the concept is not a new one. In the late nineteenth century, Dr. William B. Coley, known as the father of cancer immunotherapy, was intrigued by the recovery of one of his terminally ill cancer patients who acquired erysipelas infection and subsequently was cured of his cancer. He attempted to replicate this response in other cancer patients by infecting them with a cocktail of heat-killed bacteria. Coley’s toxins, as they were called, proved effective in many cases, but caused drastic side effects in others. What Coley did not know then was that it wasn’t the bacteria that was killing the cancer; rather, the infection triggered an immune response that was strong enough to eliminate both the pathogen and the cancer. Now that scientists are beginning to uncover the secrets of the immune system, there has been unprecedented success in the fight on cancer. Moreover, with the establishment of the Parker Institute for Cancer Immunotherapy, the top researchers in the field will be able to work together to harness the innate potential our bodies have, and to not only strengthen the fight on cancer, but also win.    

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