Much as prison guards sic bloodhounds on an escaped inmate, certain cells set the immune system's killer cells on the molecular trails of viruses or other intruders. Now researchers have created artificial cells that train the killer cells on their targets. If engineered appropriately, these artificial cells could turn the immune system against another threat, cancer.
To protect itself, the body employs its own cellular goon squad: White blood cells known as T cells seek out and kill foreign or abnormal cells. T cells become sensitized when exposed to antigens, certain molecules on the surface of threatening cells. They then go on the rampage and hunt down cells studded with similar molecules.
T cells can also sniff out antigens on cancer cells, and in experimental therapies, researchers are trying to get them to attack tumors. To do so, researchers isolate cells called dendritic cells that present antigens to T cells, rather as a prison guard waves an escapee's shirt beneath the hound's nose. Scientists combine dendritic cells with antigens from the patient's tumor and use the test tube mix to sensitize T cells, which they then inject into the patient. But dendritic cells are hard to isolate, die quickly, and must be extracted from a patient's own blood.
To avoid these complications, geneticists Michel Sadelain and Jean-Baptiste Latouche of Memorial Sloan-Kettering Cancer Center in New York City engineered artificial cells to bait the T cells. They started with mouse cells and added genes that produce antigens from either the influenza virus or melanoma tumors. They also built in genes that help dendritic cells latch onto T cells, offer up the antigen, and stimulate the T cells to multiply. When the researchers exposed T cells to these artificial cells in the lab, the T cells emerged primed to kill either cells laden with the influenza antigen or melanoma cells, they report in the April issue of Nature Biotechnology.
Molecular geneticist Paul Robbins of the University of Pittsburgh says he's surprised that mouse cells armed with a few genes can sensitize T cells as well as dendritic cells do, at least in culture dishes. The artificial cells should allow researchers to whip up batches of specialized T cells much faster than before, he says: "It's the ease of manipulations that's going to be a huge step forward."