The Methuselah Foundation. Science for the End of Aging.

Attendees at SENS3 heard first-hand about an extremely exciting approach to cancer treatment that has not yet hit the scientific literature or the press. In 2003, Dr. Zheng Cui and his colleagues at the Comprehensive Cancer Center of Wake Forest University reported the discovery of mice with immune cells that rendered them invulnerable to cancer: they had been intentionally giving mice cancer by injecting them with virulent cancer cells as part of a separate study, when they discovered a single mouse in the colony that was completely immune to the invasive cells.

His curiosity piqued, Dr. Cui went on to show that it could resist multiple rounds of such injections, and were so impressed that they used him to father a whole colony of mice, all of whom shared this remarkable invulnerability to cancer. Based on that ability, he calls them spontaneous regression/complete resistance (SR/CR) mice.

Last year, Dr. Cui electrified the world when he showed that the new strain's cancer-fighting abilities were caused by a particular subset of their immune cells -- members of a class of white blood cell known as neutrophil granulocytes. These cells are from the innate immune system, meaning that they don't have to "learn" to identify a narrowly-defined enemy, but are constantly on the lookout for broadly-defined "foreign" cells. They are a kind of phagocytic cells, surrounding, engulfing, and digesting their targets when they find them.

Dr. Cui tested the ability of these cells to fight off cancer by transfusing them into normal mice with cancers. Surprisingly, the simple transfusion of the cancer-fighting immune cells from the resistant mice effectively transfered the same remarkable protection to the normal mice. And even more excitingly, the treatment didn't just prevent cancers from forming, but actually fought off existing cancer: when researchers transfused the anti-cancer white blood cells into normal mice with existing skin tumors, the tumors regressed completely in a matter of weeks. Moreover, a single dose of the cancer-fighting immune cells gave the normal animals a cancer immunity that often lasted for the rest of their lives.

At SENS3, Dr. Cui presented the next logical step in his research: work demonstrating the existence of, and characterizing, high-potency cancer-killing granulocytes in humans.

Dr. Cui's team first went looking for the existence of potent cancer-killing granulocytes in a group of healthy volunteers. This was done by testing the volunteers' granulocytes' ability to destroy cancer cells in a petrie dish. They found that, unlike in mice (who seem to have an all-or-nothing effect), there appears to be a classical bell-shaped distribution of cancer-killing ability in the granulocytes of people in the population: a few people have white blood cells extremely weak cancer-killing activity, the great majority have an 'average' competence, and a very small group of outliers have the kind of overwhelming search-and-destroy activity (at least in a test tube!) that is seen in the SR/CR mice.

Surprisingly, they found that the ability of peoples' granulocytes to kill cancer is very sensitive to the season. Looking at the efficacy of granulocytes drawn at samples taken year round, he found that the activity is strong in the sunnier months (May to September) and falls off dramatically in the gloomier ones (November through April). The reason for this effect is unknown, but it could be connected to other things that vary with the number of hours of daylight and that are connected to cancer risk, such as the circadian-rhythm hormone melatonin or the "sunshine vitamin," vitamin D3.

He also found that the cancer-killing capacity could be "abolished" by stress: in one anecdote, a grad student from his lab at Wake Forest had been tested just after making his first presentation at a scientific conference, and the normally high level of cancer-fighting activity in his granulocytes was severely depressed. Re-testing him several days later, the activity of his granulocytes had bounced back to normal.

And, unsurprisingly, preliminary evidence suggests that cancer-fighting ability appears to fall off with biological aging, and is even lower in cancer patients. An interesting question for future research will be whether low cancer-fighting activity precedes cancer incidence (suggesting that the lack of resistance was a key factor in developing cancer) or followed it (suggesting that the disease process weakens their natural immune resistance sufficiently to overwhelm these cells' cancer-killing activity).

Based on these promising findings, Dr. Cui applied to test the transfusion of granulocytes from highly cancer-resistant people into people with existing cancer -- a potential therapy he calls "GIFT" (for "Granulocyte InFusion Therapy"). He now has approval from both the IRB and FDA to move ahead with the trial, and the next step is to raise the necessary funding.

Z. Cui, I. Molnar, M.C. Willingham, G.J. Pomper, J.R. Stehle, M. Blanks From a newly discovered innate anticancer immune response in mice to a new treatment for human cancers http://www.sens.org/sens3/abs/Cui.htm