I’ve been toying with the idea of messing with a cable TV show’s plotline. At the first season’s end of The Big C, the story’s protagonist decides to accept a harsh and usually ineffective treatment for her advanced melanoma: interleukin-2 (IL-2).
Cathy, played by the actress Laura Linney, understands the goal is not for a cure, but to temporize her disease for six months, when she might be eligible for a new melanoma drug through a clinical trial. Her oncologist has already completed the paperwork, according to the old script. The season ends with Cathy in a hospital bed with an IV catheter, presumably receiving the IL-2, and dreaming.
So I thought I’d explain a bit on interleukins and IL-2 in particular:
Interleukins are proteins defined by their capacity to communicate between different populations of white blood cells (between leukocytes). The term was put forth by a group of scientists who studied lymphocyte activation in a 1979 paper in the Journal of Immunology. IL-1 was the first named interleukin, IL-2 was the second, and so forth.
IL-2 was first known as Lymphocyte Activating Factor (LAF). It went by other names, too, including Helper Peak, T-Cell Replacing Factor III, and B-Cell Activating Factor (BAF). It’s a powerful cytokine, a molecule that stimulates other cells to grow and mature. Most of it comes from T-cells. For decades, doctors have been aware of IL-2’s anti-tumor potential: it can stimulate the body’s natural killer, lymphokine-activated killer (LAK) and other cytotoxic cells to destroy malignant cells.
Now, human IL-2 is available in recombinant form. This means that researchers don’t need to purify the stuff from growing cells. Instead, companies use its genetic sequence to manufacture the protein in commercial labs, much in the way that other hormones are synthesized for medicinal use – like insulin or growth hormone. Recombinant human IL-2 is called Aldesleukin and sold as Proleukin.
When I was a resident and a fellow, I gave IL-2 to some cancer patients and monitored their reactions in clinical trials. It’s not an easy drug to take, as is emphasized in The Big C, set to resume on TV June 27.
This year, on March 25, the U.S. FDA approved an antibody treatment for advanced melanoma: Ipilimumab (considered here), now sold as Yervoy. Just yesterday, as considered in the Pharma Strategy blog (with a helpful chart of BRAF inhibitors), Roche/Genentech submitted an application to the FDA for approval of an experimental agent, vemurafenib (aka PLX4032), for treatment of patients with advanced melanoma.
What will Cathy do? I have no idea. But it’s good to know her treatment options are broadening.