When cancer cells are injected into the mice, their white blood cells surround the tumor cells and rupture them in a process called cytolysis. The same killing process occurs when tumor cells are formed naturally by the action of carcinogens.
As the animals get older, injected cells might form a tumor, but the cancer is cleared in a day or two. The animals live a normal lifespan, about two years.
In the new study, the team took white blood cells from the immune mice -- a combination of natural killer cells, macrophages and neutrophils -- and injected them into mice already carrying a variety of tumors, some of which were extremely aggressive. In every case, the cancers were destroyed, even if the cells were injected at a point distant from the tumor. Healthy tissues were not affected.
The mice that received the cells, furthermore, were protected from new tumors for the rest of their lives. The researchers have no idea how the immunity continues.
"This is the first report of a novel [treatment] mechanism," said Dr. Andrew Raubitschek, a cancer immunologist at the City of Hope National Medical Center in Duarte. "The two most dramatic things are: one, that the response itself is outstanding, and two, the fact that they looked at a variety of different cell lines and found the activity was there for all of them."
The fact that the immunity can be transferred between mice indicates that the phenomenon is more than a simple aberration in one strain of mice and gives hope that such manipulations can lead to a therapy for humans.
"This deserves intensive follow-up," said Dr. Richard Miller of the University of Michigan Medical School. Cui's papers "are technically sound, carefully controlled and well thought out. But whenever there is a result this surprising, it's always important to have others confirm it."
Cui and his colleagues believe that the resistance results from a mutation in a single gene and are attempting to find it, but that has proved frustrating. The primary problem is that while the gene mutation may be in one location in one family of mice, it may occur on a different chromosome in another family.
"That's quite surprising to us, and we are still trying to pin it down," Cui said.
The Cancer Research Institute in New York City, which is the primary sponsor of Cui's research, has brokered a collaboration with Dr. Bruce Beutler at the Scripps Research Institute in La Jolla and immunologist Robert D. Schreiber of the Washington University School of Medicine in St. Louis to try to identify the gene.
