Using the Immune System to Fight Melanoma (Part Two – Potential)

My previous post talked about the history of using the immune T-cells in the fight against cancer. I’m picking up the thread of the story where the human experiments began…

A small pharmaceutical company approached by researcher Jim Allison, Medarex, decided to begin human trials using patients diagnosed with malignant melanoma. Melanoma sometimes responds to immunotherapy treatment. The first experiments focused on CTLA-4, using antibodies to turn off the response of the protein on the T-cells. A few of the human cancer tumors shrank during the pilot. Encouraging news, right? But the problem was that in most of the trials, the tumors would continue to grow after the trial period. It was only after doctors still treating the patients realized that months after the treatment phase that the tumors were actually shrinking. The experiments just needed more time than radiation to work.

The upshot after the study was extended? A quarter of the patients treated with CTLA-4 antibodies were alive two years into the trial when they were only given seven months. Twenty-four months versus seven! That’s remarkable. As Allison is quoted in the article, “it was the first drug of any type to show a survival benefit in advance melanoma patients in a randomized trial.” In 2011, Nature reported that CTLA-4 antibody “provides realistic hope for melanoma patients, particularly those with late-stage disease who otherwise had little chance for survival.”

The article is fascinating not only because of the science involved, but the patient stories related as well. It talks about a 22-year old woman diagnosed with metastatic melanoma who showed no lesions on her skin, and yet it invaded her chest and then eventually her brain. She received interleukin-2, a treatment designed to stimulate the T-cells. It failed. She was given the news that she had very limited time left. But then she received the experimental CTLA-4 treatment. Don’t get me wrong, the side effects sounded awful – an attack on her thyroid, night sweats, terrible body aches. But after four treatments given every three weeks, the tumors in her lungs were shrinking.

Eight years later, she is showing no signs of cancer. Eight freaking years. For someone in late-stage metastatic melanoma, that’s like being given a lifetime. Even if she now has to take medication because of the damage the immune response did to her thyroid.

That’s the rub with this type of treatment – it can cause the immune system to attack things other than the cancer it should be targeting. But when you are literally staring death in the face, that may be a trade-off patients are willing to make. Particularly when chemo and radiation also do such collateral damage to the body as well.