Natural Cancer Resistance in Mice and in Humans: basis for a novel cancer therapy

Zheng Cui, Mark C Willingham, Yikong Keung, Gregory Pomper, John Stehle, Michael Blanks and Lisa Kim-Shapiro
Section of Tumor Biology, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC

Why don't intentional exposures to known carcinogens, such as cigarette smoking, always cause lung cancer for most people? Living well into very old ages with heavy smoking but without getting lung cancer is not likely due to just being lucky. It is highly likely that most humans are protected intrisically by an innate mechanism to confront cancer cells. If cancer is associated with a decline of such a protection mechanism, restoring this activity may offer a new avenue for cancer treatment.

In 1999, we encountered a unique mouse that refused to succumb to repeated challenges with lethal cancer cells that uniformly killed all other laboratory mice, even at much lower doses. Further studies of this phenotype reveal that this unusual cancer resistance is inheritable and entirely mediated by the macrophages and neutrophils of the innate immunity. Transfer of leukocytes with this high level of cancer-killing activity (CKA) from these cancer-resistant mice cures the most aggressive advanced cancers in other mice without any side effect. Most surpisingly, a similar activity of killing cancer cells was discovered in the granulocytes and monocytes of some healthy people.

Additional studies also indicate that CKA is highly dynamic in human populations. CKA is affected profoundly by individual genetic make-ups, by different seasons, by different ages and by emotional stresses. More importantly, low CKA has a significant association with cancer patients in comparison to healthy people. It seems reasonable to believe that cancers can be treated by transferring granulocytes, an abundant white cell fraction that contains the most CKA, from cancer-resistant human donors to cancer patients. This new therapeutic concept is significantly different from the conventional immunotherapies based on the attempts to revive cancer patients' own adaptive immunity to fight their own cancers.

Now, a new clinical trial is underway at Wake Forest University to test this novel cancer therapy, termed "Leukocyte Infusion Therapy" or LIFT. This clinical trial has met all regulatory requirements including approval by the Wake Forest University School of Medicine's Institutional Review Board (IRB) and been granted an IND (Investigational New Drug) status by the Food and Drug Administration (FDA).

Keywords: Cancer-resistance, Granulocyte, Cancer therapy, Clinical trial, LIFT