“My dad is in the hospital,” my friend said softly. “The doctors aren’t really sure what’s wrong, so they’re doing a bunch of tests.” We called and texted in between lab tests, waiting pensively. When I heard the final diagnosis—Stage III/IV cancer, metastatic melanoma—my heart sank. My friend was in the midst of a flurry of calls for her wedding, which was coming up soon. The clock kept ticking. I took a deep breath—then I got up to check on my flask of melanoma cells growing steadily in the 37-degrees Celsius incubator.
I am a MD/PhD student currently in graduate school studying immunology. In medical school, I was fascinated by the immune system, an adaptable army of cells designed to recognize when something is not quite right and eradicate the offending pathogens – viral infection, tuberculosis… even cancer cells.
Physicians noticed as early as the late 1800s that the body’s immune system, primarily evolved to fight off infections, could also attack tumors and kill cancer cells. Dr. William Coley, pioneer of cancer immunotherapy, noticed that cancer patients who got infections after surgery had better outcomes compared to those that did not get sick. He suspected it was because infections tickled the immune system just enough to mount a robust, generalized response. To boost his patients’ anti-cancer immune responses, Coley tried directly injecting various doses of live bacteria into cancer patients. Although his experiments were incredibly risky, Coley treated over 1,000 patients with bone cancer, reportedly inducing tumor regression in many.
Despite Dr. Coley’s astute observations, other oncologists were not impressed with the inconsistencies in Coley’s methods and turned to other, more exciting treatments of the early 1900s like radiation. It took almost another century for doctors and researchers to reach two important conclusions. First, the immune system is actually capable of recognizing cancers as “foreign,” even though cancers originate from the body’s own tissues. Second, boosting the immune response can enhance other cancer-killing agents. Oncologists and researchers now face two major challenges: to figure out which therapies work best for which cancers, and why some cancer patients respond better than others.
Today, an oncologist has several options for cancer immunotherapies. Some treatments provoke a general immune response—what Coley had intended with his bacterial injections. Other treatments are more precise: antibodies recognize and bind to specific proteins on cancer cells or immune cells, refining and focusing the immune response. There are even cancer vaccines that can be used to prevent or treat cancers by stimulating the body’s own defenses. Unfortunately, current treatments are not enough. More than 80 percent of metastatic melanoma patients die within five years of their initial diagnosis.
As my friend’s dad got sicker, I felt a growing impatience with my own work. I had begun my research in the hopes of one day contributing to the next cancer immunotherapy. But despite years of work, patients like him are still waiting for these treatments to materialize. Why does it take so long for new therapies to become available, despite decades of research, for patients that desperately need them? On my worst days, when every experiment isn’t working the way I had hoped, I feel infinitely small. How can I begin to wrap my head around improving cancer treatment, let alone curing it?
To ensure the safety of future patients, clinical researchers test a new drug in multiple steps, or phases. The final hurdle to approving a drug, a phase III clinical trial, is designed to answer whether the new drug works better than what is already available on the market. The cancer immunotherapy ipilimumab is particularly remarkable because it was the first drug to show demonstrable benefit compared to chemotherapy, the standard of care for over 30 years for melanoma patients. This powerful drug, however, is a double-edged sword. Just as chemotherapies can have devastating effects on the rest of the body, immunotherapies have their share of side effects. For example, ipilimumab stimulates immune cells to shrink tumors, but its effects aren’t confined there. Immune cells in the intestinal tract, liver and skin also attack healthy tissues, often with severe consequences.
It’s easy to be pessimistic about the plodding, slothful pace of research and drug development. Yet, the dire need for better treatments has pressured the FDA to revise its policies in order to rapidly approve new drugs for melanoma. Policy changes coupled with groundbreaking research have led to a wave of new immunotherapies in the last five years alone. We haven’t cured melanoma yet, and researchers like me are trying to understand the finer details of how the immune system interacts with cancers. But now we know that immunotherapy can extend lives of patients for months or even years. Enough time for my friend’s dad to walk her down the aisle.