TMC PULSE

t m c » p u l s e | j u n e 2 0 1 5 16 Over the past year alone, the FDA approved two immunotherapy drugs for use in melanoma treatment, and in March, one of the drugs was also approved for lung cancer treatment. The field of immunotherapy is not new, but this swift progress comes after years of disappointment and unmet potential. Just as hope for the future of immunotherapy began to fade, ground- breaking discoveries made by James P. Allison, Ph.D., chair of the immunology department at The University of Texas MD Anderson Cancer Center, transformed it into one of the most promising frontiers of cancer treatment. The idea of using a patient's own immune system to fight cancer dates back to the late 1800s. Like so many great medical advance- ments before and after, the discovery of immunotherapy happened largely due to chance. William B. Coley, M.D., a bone surgeon at Memorial Hospital in New York City, noticed that cancer patients who developed bacterial infections after undergoing surgery fared better than other patients. He hypothesized the infection awakened the immune system, which then fought off cancer cells while also fighting the infection. Coley tested his theory by injecting bacteria in patients with inoperable cancerous tumors. He achieved successes with the method— notably, one young patient with a malignant tumor survived another 26 years after Coley injected him with "Coley toxins." Surgery, Allison explained, requires early detection—if you can't get all the tumors before the cancer spreads, surgery is not curative. Radiation treatment poses the same problem. Chemotherapy is successful in curing certain types of cancers, but brings with it terrible side effects. Still, the triumphs of these forms of treatment caused immunotherapy to fall by the wayside, in part because there seemed to be a missing piece in the puzzle of how to achieve a durable immune response. That changed in the 1990s, when Allison and his team found that a molecule on T-cells, the immune system's attack cells, acts as a brake on the immune response. Before Allison's discovery, "we didn't under- stand the basic biology of how T-cells were regulated," said Padmanee Sharma, M.D., Ph.D., professor of genitourinary medical oncology and immunology at MD Anderson. "We tried to give vaccines to turn on the T-cells and attack the tumor, but they didn't work." For years, clinical trials focused on engaging T-cell receptors failed. The immune system would respond for a time, but would eventually shut off. No one understood why, until Allison and other researchers identified the first set of brakes on T-cells, CTLA-4, now known as a "checkpoint molecule." F I G H T I N G C A N C E R from W I T H I N G R O U N D B R E A K I N G D I S C O V E R I E S M A D E B Y M D A N D E R S O N ' S J A M E S P. A L L I S O N , P H . D. , A R E R E V I TA L I Z I N G T H E F I E L D O F C A N C E R I M M U N O T H E R A P Y. Allison and the researchers at his MD Anderson labs are seeking new checkpoint targets, as well as more effective combinations of treatments. Coley's work created the foundation for the immunotherapy of today, but years passed before significant progress was made in the field. By the early 1900s, radiation therapy entered the scene and quickly became the go-to treatment, alongside surgery. In the 1960s, chemotherapy became the third pillar of treatment. "These are the three modalities that have persisted," said Allison. "But of course, they have things wrong with them." B y S h e a C o n n e l ly F or decades, the standard of care in cancer treatment consisted of three major pillars: surgery, radiation and chemotherapy. In recent years, however, another type of treatment—immunotherapy—has grown in leaps and bounds, offering new hope to cancer patients around the world.

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