Using the Immune System to Fight Melanoma (Part One – Background)

Disclaimer: I’m a science nerd. I love the compilations like the Best American Science and Nature Writing. I got the 2013 edition out of the library and there was an article, originally published in The New Yorker, entitled The T-Cell Army.

The article discussed the history of Dr. William Coley, a surgeon in 1890s New York City who lost a patient due to sarcoma, a cancer of the connective tissue. In an attempt to find out how to better treat patients like this, he discovered the case of an immigrant, Fred Stein, who had been diagnosed with a “hopeless” case of sarcoma. But then Stein came down with a streptococcal bacterial infection – and in the 1890s, there were no antibiotics. While Stein’s immune system fought off the infection, it also caused his sarcoma to shrink to the point where the cancer was no longer discernible.

Coley faced a lot of criticism for postulating that the immune system could help fight cancer. He was working at the same time as James Ewing, who believed that radiation was the only scientific way to treat cancer. Obviously, we know who won the public relations battle and radiation became the de facto standard for cancer treatments.

But in the 1970s, a researcher at the University of Texas Cancer Center thought that maybe the immune system, in particular, the T-cells, deserved another look. Jim Allison faced a lot of discouragement, telling him that his line of research would amount to nothing. However, Allison discovered something crucial – to be effective, T-cells require two signals. When targeting bacteria or a virus, the t-cells get both signals. But in the presence of cancer, those signals are absent.

Adding to the story, there is a protein with a very long scientific name that gets shortened to CTLA-4 that is on the surface of the T-cells. For awhile, researchers weren’t too sure what this protein did. Allison’s team of researchers injected an antibody that blocked CTLA-4 into mice that were also injected with cancer cells. After a few weeks, the cancer in the mice disappeared. Allison and his team repeated these experiments over the course of a few years to ensure that the results weren’t a fluke, that there really was something happening to shrink and then eliminate the cancer in the mice. But the only way to know for sure if it actually worked in humans was to try the experiment in humans…