Z. Cui, I. Molnar, M.C. Willingham, G.J. Pomper, J.R. Stehle, M. Blanks

While most of the research attention has been focused on the question, why cancer occurs in about 25% of humans, a less frequently asked question has been why the other 75% of humans do not get cancer. Cigarette-smoking is a highly reliable way for humans to expose themselves to known carcinogens, causing a 100-fold increase of lung cancer rates from 0.08% in the general population to 8% in smokers. Why do the other 92% of smokers not get cancer? It has long been speculated that there is a cancer surveillance system in humans. There must be something that protects healthy humans from getting cancer, even after repeated exposures to carcinogens. It must be something that removes cancer cells before they can form clinical lesions and more importantly, it must be something that can protect the hosts against cancer cells inherently and naturally. The discovery of cancer-resistant mice 9 years ago and subsequent studies indicated that such a natural cancer resistance existed in a very small number of laboratory mice and was inheritable. The mechanism of such a natural cancer resistance is mediated by a dominant inheritance that activates the innate immune response. Neutrophils and macrophages, as major components of infiltrating leukocytes, migrate to the site of cancer cells, capture the cancer cells by making tight physical contact with the cancer cell surface and destroy them via cytolysis. The leukocytes of these cancer-resistant mice can be used as therapeutic agents to cure several forms of highly aggressive cancers in wild type mice without any sign of adverse side effects. This leads to the apparent question of whether we can find cancer-resistant humans to test a similar cancer treatment via allogenic innate white cell transfer. Using a newly developed in vitro assay to measure the ability of white cells to kill various cancer cell line targets, we surveyed human volunteers and found that a significant number of healthy humans have cancer-killing activity (CKA) similar to that of cancer-resistant mice. There seems to be a bell-shaped distribution of CKA in the population of healthy humans. The CKA average appears to be lower in older human populations and to be even lower in human cancer patients. The CKA can also be abolished by stress and change of seasons. Based on these findings and the ability to screen for cancer-resistant humans as allogenic white cell donors, we proposed a new cancer treatment strategy, termed "GIFT" (Granulocyte InFusion Therapy), that will soon enter phase II clinical trials.

Keywords (Optional): 
cancer therapy
innate immunity