Imagina

This thought inspired recent work by James Hansen, a Yale professor of therapeutic radiology. Hansen transformed lupus autoantibodies — immune system proteins that fight normal proteins to cause lupus — into selective vehicles for drug delivery and cancer therapy.

His focus was 3E10, an autoantibody associated with lupus. Hansen and his team knew that 3E10 is able to penetrate into a cell’s nucleus to inhibit DNA repair and spark symptoms of disease. What remained a mystery was the exact mechanism by which 3E10 accomplishes nuclear penetration, and why the autoantibody is apparently selective for tumor cells. Unlockign these scientific secrets opened up new possibilities to counteract disease, namely, by protecting the very cells that the autoantibody might attack.

“Now that we understand how [3E10] penetrates into the nucleus of live cells in a DNA

dependent manner, we believe we have an explanation for the specific targeting of the antibody to

damaged or malignant tissues where DNA is released by dying cells,” Hansen said.

What Hansen’s team found was that 3E10’s ability to penetrate efficiently into a cell nucleus is dependent on the presence of DNA outside cell walls. When solutions absent of DNA were added to cells incubated with 3E10, no nuclear penetration occurred. With the addition of purified DNA to the cell solution, nuclear penetration by 3E10 was induced immediately. In fact, the addition of solutions that included DNA increased nuclear penetration by 100 percent. The researchers went on to show that the actions of 3E10 also rely on the ENT2 nucleoside transporter. Once bound to DNA outside of a cell, the autoantibody can be transported into the nucleus of any cell by the ENT2 nucleoside transporter.