White Blood Cells Obtained From Healthy Donors To Be Tested Against Human Malignant Cancers

“Granulocytes obtained from healthy donors could eradicate malignant cells in patients with cancer, according to researchers at Wake Forest University Comprehensive Cancer Center, in Winston-Salem, North Carolina. They will be evaluating this novel strategy, called leukocyte infusion therapy (LIFT), in a phase 2 clinical trial designed to determine whether it is as effective at eliminating cancer in humans as it has proven to be in mice.”

“Granulocytes obtained from healthy donors could eradicate malignant cells in patients with cancer, according to researchers at Wake Forest University Comprehensive Cancer Center, in Winston-Salem, North Carolina. They will be evaluating this novel strategy, called leukocyte infusion therapy (LIFT), in a phase 2 clinical trial designed to determine whether it is as effective at eliminating cancer in humans as it has proven to be in mice.

‘The purpose of this trial is to test a new concept, and to see whether or not it works,’ lead author Zheng Cui, MD, PhD, associate professor of pathology, told Medscape Oncology. ‘We know that it is highly effective in mice, but don’t know if the same applies to humans. But if we don’t test it, we will never know.’

The LIFT trial will examine 22 patients with cancer who cannot be treated with conventional therapies; each patient will receive daily allogeneic white blood cell infusions. If the treatment is effective, there will be a rapid response rate because granulocytes are short-lived cells. ‘If we don’t see a response within 3 to 4 weeks, then we probably aren’t going to see one,’ said Dr. Cui.

Cancer-Resistant Mouse

Nearly a decade ago, Dr. Cui and colleagues identified a unique laboratory mouse that appeared to be completely resistant to repeated challenges with lethal cancer cells. The mouse resisted very high doses of cancer cells that uniformly killed all other laboratory mice, even when given at much lower doses.

The phenomenon was intriguing, and further study revealed that this unusual cancer resistance was an inherited trait, mediated entirely by the macrophages and neutrophils of the innate immunity. The cancer-resistance trait has been passed on to more than 2,000 descendants in 14 generations, and has also been bred into 3 other mouse strains. Approximately 40% of each generation inherits the mechanism that seemingly protects them from developing cancer.

Research published in 2006 (Proc Natl Acad Sci U S A. 2006;103:7753-7758) showed that the resistance was completely transferable. Transferring splenocytes, bone marrow cells, or enriched peritoneal macrophages from resistant to normal mice not only protected them from what should have been lethal doses of new cancers, it also cured the most aggressive advanced malignancies. The type of malignancy did not seem to matter, and the transferred white blood cells did not appear to cause any adverse events.

Duplication in Humans

Research indicates that the anticancer components of white blood cells are highly dynamic in human populations, but can be significantly affected by a number of factors, Dr. Cui pointed out. The cancer-killing activity observed in white blood cells is lower in cancer patients than in healthy people. It is also lower in older people, during the winter months, and during times of emotional stress. In humans, granulocytes and monocytes display the highest levels of cancer-killing activity; this is very similar to what the researchers have observed in the cancer-resistant mice.

‘For our human trial, the key is to select the donors according to the therapeutic properties that we are looking for,’ said Dr. Cui. ‘Ideally, we hope to set up a donor registry.’

At startup, 500 potential donors, 50 years or younger and in good health, will be recruited. The cancer-killing activity of their granulocytes will be measured in vitro, and white blood cells will be harvested from the donors with the highest levels of activity.

The trial will be limited to 22 patients with cancer that is untreatable by conventional methods. ‘That is the most important selection criteria,’ said Dr. Cui, ‘that these are not patients who could possibly benefit from available therapies.’

Patients selected for participation will receive 5 to 10 daily allogeneic white blood cell infusions. To assess in vitro cancer-cell-killing activity, blood samples will be evaluated before the first infusion, immediately after the first infusion, on day 2, and then immediately after the last infusion. If tumor tissue is readily accessible, such as in the axillary lymph nodes or subcutaneous tumor nodules, a biopsy will be performed during the first week of treatment to demonstrate the presence or absence of tumor-infiltrating granulocytes.

Not a Cure…Yet

Reactions to the upcoming trial have been somewhat mixed, Dr. Cui explained. Some researchers have been excited about the possibility of success; others have expressed skepticism about moving from animal models to human trials before fully investigating the exact mechanisms involved.

But Dr. Cui and colleagues believe that they should move forward with human clinical trials, rather than spend years trying to determine the underlying mechanism of action. ‘If we can identify the cancer-resistant humans, then why not just do the same thing as we did in mice, and try to find out whether it will work or not,’ he said. ‘Granulocytes have been successfully and safely used for over 30 years to treat infectious diseases, so we know that it has limited toxicity.’

However, Dr. Cui emphasized that they have not found a cure for cancer. ‘This therapy is unique and worked extremely well in mice, even with malignancies that could not be cured with conventional therapies,’ he said. ‘But now we have to see if it works as well in people.’

Co-researcher Mark Willingham, MD, professor of pathology, agrees. ‘If the study is effective, it will be another arrow in the quiver of treatments aimed at cancer,’ he said in a statement. ‘It is based on the 10 years of work conducted since the cancer-resistant mouse was first discovered.’”

Quoted Source: Novel Cancer Therapy Moving to Human Trials (Free Registration Required), by Roxanne Nelson, Medscape Medical News, Medscape Hemotology-Oncology, July 3, 2008.

Additional Information:

• Leukocyte Infusion Therapy Clinical Trial Description, Wake Forest University Baptist Medicial Center.
• Leukocyte Infusion Therapy Clinical Trial Protocol.