Research finding could lead to more effective cancer vaccines
Gene therapy harks back to old theory on immune system function

By Robert Sanders, Public Affairs

26 September 2001 | Insertion of a single gene into several different tumors enabled mice to reject them all, leading scientists at Berkeley to hope that the gene might form the basis for a vaccine effective against a range of cancers.

This simple gene therapy also protected the mice against subsequent injection of tumor cells that had not been altered, meaning their immune systems remembered the initial challenge — a necessary step for any vaccine therapy.

“When we introduced the gene into cells that didn’t have it and then injected the tumor cells into mice, they clearly stimulated a variety of different elements of the immune system, including natural killer cells and killer T cells,” said David Raulet, the Choh Hao Li Professor of Immunology in the College of Letters & Science. “The response in mice was really very dramatic and unexpected — the tumors were all uniformly rejected.”

He is optimistic that the gene — actually two families of similar genes — will make an effective vaccine therapy, joining the growing arsenal of cancer immunotherapies in clinical trials today.

Raulet, along with postdoctoral fellow Andreas Diefenbach, graduate student Amanda Jamieson and postdoctoral fellow Eric Jensen, reported the findings in the Sept. 13 issue of Nature. All are part of the campus’s Health Sciences Initiative.

The findings hark back to a theory popular a generation ago — that the immune system constantly surveys the body for cancer cells and kills them on sight. Only when the growth of cancer cells outstrips the immune system’s ability to eliminate them do tumors form.

The idea fell by the wayside when scientists found that most cancers were no more common in mice lacking certain components of the immune system than in normal mice. More recent studies, however, suggest that the mice used in the first reports were not entirely immunodeficient, and that cancer is indeed more common in immunodeficient mice.

One way the immune system could detect tumors is if cells in the process of converting into cancer cells put up flags, or protein markers, that alert the immune system and draw its fire. The protein products of the genes that Raulet and his team have identified could be one of these common flags.

“The surveillance theory may be on the rebound,” Raulet said. “The immune system may be cleaning up many tumors, but we haven’t, until now, had the tools to see this.”

Raulet and his laboratory colleagues found the proteins while pursuing their main interest, natural killer cells.

These generalized attack cells of the immune system are among the first and fastest line of defense against invading tumors and viruses and keep them at bay until the more specialized T and B cells have had a chance to ramp up production.