Seattle, April 1, 2002 / Pacific Northwest Research Institute

PACIFIC NORTHWEST RESEARCH INSTITUTE REPORTS DRAMATIC SUCCESS IN CANCER IMMUNOTHERAPY

Scientists at the Pacific Northwest Research Institute (PNRI, now PNDRI) in Seattle have created a method to make the immune system more powerful in destroying tumors. It is described in an April 1 Nature Medicine article, first-authored by Dr. Zhengmao Ye.

According to the study, tumors that were established from a highly malignant mouse melanoma were rejected in mice that were given a therapeutic vaccine. These tumors are similar to many human cancers in that they lack the machinery needed for recognition by the immune system. Such tumors were previously considered untreatable by tumor vaccination.

PNRI researchers inserted genes encoding artificially constructed antibody fragments into the tumor cells. These fragments (scFv) created ligands on the surface of the cancer cells, binding them to lymphoid cell molecules that can stimulate the immune system. Mice with tumors growing under the skin or in their lungs were vaccinated with the modified cells. Most of the treated mice became completely cancer free.

In a Nature Medicine editorial, Dr. Leiping Chen, Professor of Immunology at the Mayo Clinic, heralds the promise of this study. It pioneers a gene therapy that strengthens the signals needed to turn immune cells against growing tumors even when they have very low immunogenicity.

According to Karl Erik Hellstrom, the paper's senior author, the elusiveness of cancer cells is what makes them so hard to fight. "Immunological differences between most cancer cells and normal cells are very slight," Hellstrom says. "The body is geared toward avoiding immunological reactions that can destroy normal tissues. So better ways to induce a strong and selective anti-tumor response are needed."

Jeffrey Ledbetter, a key member of the PNRI research team, points to the value of their innovative technology. "Nature has never done it this way," Ledbetter says. "The artificial ligands we created are stronger and more active than natural ligands. So they trigger the immune system to destroy the cancer."

Study scientists are hopeful about the eventual application of this approach to human cancers. But they also acknowledge that there is much still to discover about the cellular mechanisms underlying these remarkable laboratory results.