Tandem Attack

SAN DIEGO — By attaching a tumor-suppressing protein to an innocuous compound, scientists have devised a way to insert the valuable cargo into malignant cells and kill them. The findings, in mice, have paved the way for preliminary testing of the drug in people with cancer.

Cells can turn cancerous in part because they are missing natural cancer-inhibiting proteins. Researchers at Trojantec Ltd. in Nicosia, Cyprus, teamed with scientists at Imperial College London to attach a tumor-suppressor protein called p21 to a harmless peptide called antennapedia.

They chose antennapedia because it has the ability to pass through cell membranes like a ghost through a wall. In this way, it can drag p21 inside, says Christina Kousparou, a molecular biologist at Trojantec, who presented the results in San Diego on April 15 at a meeting of the American Association for Cancer Research.

In tests in mice, the scientists found that the tandem compound infiltrated cells throughout the animals’ bodies. Since cells normally have p21, most were unaffected.

But roughly half of human cancers lack p21, Kousparou says, and lab tests had shown that adding it slams on the brakes of cell growth. When a malignant cell suddenly changes its growth behavior this way, it attracts the attention of immune cells, which destroy it, Kousparou says.

The researchers found that all mice with cancer receiving daily infusions of the dual compound showed significant tumor shrinkage and prolonged survival. In about 40 percent of the mice, the treatment eradicated the cancer. The scientists have tested ovarian, colon and bone cancers so far. All responded to the treatment.

Antennapedia is actually a fruit fly compound. “But it resembles mammalian proteins, so the cell doesn’t attack it,” Kousparou says. “The cell doesn’t know it’s dragging things along that could potentially kill it. In that way, it resembles a Trojan horse.”

For now, the prospective drug is called simply antennapedia ‘trojan’ peptide. It would hypothetically work in people who have cancers in which p21 is dysfunctional.