Cancer News

ScienceDaily (June 30, 2008) — Scientists at Wake Forest University Baptist Medical Center are about to embark on a human trial to test whether a new cancer treatment will be as effective at eradicating cancer in humans as it has proven to be in mice.

The treatment will involve transfusing specific white blood cells, called granulocytes, from select donors, into patients with advanced forms of cancer. A similar treatment using white blood cells from cancer-resistant mice has previously been highly successful, curing 100 percent of lab mice afflicted with advanced malignancies.

Zheng Cui, Ph.D., lead researcher and associate professor of pathology, will be announcing the study June 28 at the Understanding Aging conference in Los Angeles.

The study, given the go-ahead by the U.S. Food and Drug Administration, will involve treating human cancer patients with white blood cells from healthy young people whose immune systems produce cells with high levels of cancer-fighting activity.

The basis of the study is the scientists’ discovery, published five years ago, of a cancer-resistant mouse and their subsequent finding that white blood cells from that mouse and its offspring cured advanced cancers in ordinary laboratory mice. They have since identified similar cancer-killing activity in the white blood cells of some healthy humans.

“In mice, we’ve been able to eradicate even highly aggressive forms of malignancy with extremely large tumors,” Cui said. “Hopefully, we will see the same results in humans. Our laboratory studies indicate that this cancer-fighting ability is even stronger in healthy humans.”

The team has tested human cancer-fighting cells from healthy donors against human cervical, prostate and breast cancer cells in the laboratory — with surprisingly good results. The scientists say the anti-tumor response primarily involves granulocytes of the innate immune system, a system known for fighting off infections.

Granulocytes are the most abundant type of white blood cells and can account for as much as 60 percent of total circulating white blood cells in healthy humans. Donors can give granulocytes specifically without losing other components of blood through a process called apheresis that separates granulocytes and returns other blood components back to donors.

In a small study of human volunteers, the scientists found that cancer-killing activity in the granulocytes was highest in people under age 50. They also found that this activity can be lowered by factors such as winter or emotional stress. They said the key to the success for the new therapy is to transfuse sufficient granulocytes from healthy donors while their cancer-killing activities are at their peak level.

For the upcoming study, the researchers are currently recruiting 500 local potential donors who are 50 years old or younger and in good health to have their blood tested. Of those, 100 volunteers with high cancer-killing activity will be asked to donate white blood cells for the study. Cell recipients will include 22 cancer patients who have solid tumors that either didn’t respond originally, or no longer respond, to conventional therapies. The study will cost $100,000 per patient receiving therapy, and for many patients (those living in 22 states, including North Carolina) the costs may be covered by their insurance company. There is no cost to donate blood.

For more information about qualifications for donors and participants, go to http://www.wfubmc.edu/LIFT (Web site will be available the evening of 6/27.) Cancer-killing ability in these cells is highest during the summer, so researchers are hoping to find volunteers who can afford the therapy quickly.

“If the study is effective, it would be another arrow in the quiver of treatments aimed at cancer,” said Mark Willingham, M.D., a co-researcher and professor of pathology. “It is based on 10 years of work since the cancer-resistant mouse was first discovered.”

Volunteers who are selected as donors — based on the observed potential cancer-fighting activity of their white cells — will complete the apheresis, a two- to three-hour process similar to platelet donation, to collect their granulocytes. The cancer patients will then receive the granulocytes through a transfusion — a safe process that has been used for more than 30 years. Normally, the treatment is used for patients who have antibiotic-resistant infectious diseases. The treatment will be given for three to four consecutive days on an outpatient basis. Up to three donors may be necessary to collect enough blood product for one study participant.

“The difference between our study and the traditional white cell therapy is that we’re selecting the healthy donors based on the cancer-killing ability of their white blood cells,” said Cui. The scientists are calling the therapy Leukocyte InFusion Therapy (LIFT).

The goal of the phase II study is to determine whether patients can tolerate a sufficient amount of transfused granulocytes for the treatment. Participants will be monitored on a regular basis, and after three months scientists will evaluate whether the treatment results in clear clinical benefits for the patients. If this phase of the study is successful, scientists will expand the study to determine if the treatment is best suited to certain types of cancer.

Yikong Keung, M.D., a medical oncologist, is the chief clinical investigator of the study. Gregory Pomper, M.D., assistant professor of pathology and the director of the Wake Forest Baptist blood bank, will oversee the blood banking portion of the study.

Some types of chemotherapy make it harder for your bone marrow to produce new white blood cells. White blood cells help your body fight infection. Therefore, it is important to avoid infections, since chemotherapy decreases the number of your white blood cells.

There are many types of white blood cells. One type is called neutrophil. When your neutrophil count is low, it is called neutropenia. Your doctor or nurse may do blood tests to find out whether you have neutropenia.

It is important to watch for signs of infection when you have neutropenia. Check for fever at least once a day, or as often as your doctor or nurse tells you to. You may find it best to use a digital thermometer. Call your doctor or nurse if your temperature is 100.5°F or higher.

• Your doctor or nurse will check your white blood cell count throughout your treatment. If chemotherapy is likely to make your white blood cell count very low, you may get medicine to raise your white blood cell count and lower your risk of infection.
• Wash your hands often with soap and water. Be sure to wash your hands before cooking and eating, and after you use the bathroom, blow your nose, cough, sneeze, or touch animals. Carry hand sanitizer for times when you are not near soap and water.
• Use sanitizing wipes to clean surfaces and items that you touch. This includes public telephones, ATM machines, doorknobs, and other common items.
• Be gentle and thorough when you wipe yourself after a bowel movement. Instead of toilet paper, use a baby wipe or squirt of water from a spray bottle to clean yourself. Let your doctor or nurse know if your rectal area is sore or bleeds or if you have hemorrhoids.
• Stay away from people who are sick. This includes people with colds, flu, measles, or chicken pox. You also need to stay away from children who just had a “live virus” vaccine for chicken pox or polio. Call your doctor, nurse, or local health department if you have any questions.
• Stay away from crowds. Try not to be around a lot of people. For instance, plan to go shopping or to the movies when the stores and theaters are less crowded.

• Be careful not to cut or nick yourself. Do not cut or tear your nail cuticles. Use an electric shaver instead of a razor. And be extra careful when using scissors, needles, or knives.
• Watch for signs of infection around your catheter. Signs include drainage, redness, swelling, or soreness. Let your doctor or nurse know about any changes you notice near your catheter.
• Maintain good mouth care. Brush your teeth after meals and before you go to bed. Use a very soft toothbrush. You can make the bristles even softer by running hot water over them just before you brush. Use a mouth rinse that does not contain alcohol. Check with your doctor or nurse before going to the dentist. (For more about taking care of your mouth, see Mouth and Throat Changes.)
• Take good care of your skin. Do not squeeze or scratch pimples. Use lotion to soften and heal dry, cracked skin. Dry yourself after a bath or shower by gently patting (not rubbing) your skin. (For more information about taking care of your skin, see Skin and Nail Changes.)
• Clean cuts right away. Use warm water, soap, and an antiseptic to clean your cuts. Do this every day until your cut has a scab over it.
• Be careful around animals. Do not clean your cat’s litter box, pick up dog waste, or clean bird cages or fish tanks. Be sure to wash your hands after touching pets and other animals.
• Do not get a flu shot or other type of vaccine without first asking your doctor or nurse. Some vaccines contain a live virus, which you should not be exposed to.
• Keep hot foods hot and cold foods cold. Do not leave leftovers sitting out. Put them in the refrigerator as soon as you are done eating.

• Wash raw vegetables and fruits well before eating them.
• Do not eat raw or undercooked fish, seafood, meat, chicken, or eggs. These may have bacteria that can cause infection.

• Do not have food or drinks that are moldy, spoiled, or past the freshness date.
• Call your doctor right away (even on the weekend or in the middle of the night) if you think you have an infection. Be sure you know how to reach your doctor after office hours and on weekends. Call if you have a fever of 100.5°F or higher, or when you have chills or sweats. Do not take aspirin, acetaminophen (such as Tylenol®), ibuprofen products, or any other drugs that reduce fever without first talking with your doctor or nurse. Other signs of infection include:
  • Redness
  • Swelling
  • Rash
  • Chills
  • Cough
  • Earache
  • Headache
  • Stiff neck
  • Bloody or cloudy urine
  • Painful or frequent need to urinate
  • Sinus pain or pressure

ScienceDaily (Jul. 26, 2007) — Cancer patients who receive a drug that stimulates the growth of infection-fighting white blood cells may be significantly less likely to die from a chemotherapy-related complication characterized by fever and low white blood cell levels, according to a multi-institutional study led by researchers from the University of Rochester School of Medicine and Dentistry and the Duke Comprehensive Cancer Center.

“Chemotherapy drugs target cancer cells, but they can affect healthy cells as well, including infection-fighting white blood cells,” said Nicole M. Kuderer, M.D., a hematology-oncology fellow at Duke and lead author on the publication. “When patients’ white blood cell counts drop too low, they are at risk for dangerous infections that can cause death.”

Often, chemotherapy must be delayed, reduced in strength or halted when a patient’s white blood cell count is too low, potentially leading to poorer outcomes, she added.

“Patients taking a drug known as granulocyte colony-stimulating factor early in their chemotherapy were about half as likely to develop dangerously low white blood cell counts with fever, and half as likely to die from infection,” Kuderer said. “This study represents an important part of the effort to better treat this common complication in cancer patients receiving chemotherapy.”

The researchers published their findings in the July 20, 2007 issue of the Journal of Clinical Oncology. The work was part of research being conducted by the Awareness of Neutropenia in Chemotherapy (ANC) Study Group, a multi-institution, university-based network of investigators whose work is unrestrictedly funded by Amgen, the maker of a commonly utilized white blood cell booster that goes by the names Neupogen and Neulasta. Kuderer also receives funding from the National Institutes of Health.

This study compiled the results of 17 trials involving more than 3,000 patients receiving chemotherapy of varying intensity to treat several different types of cancers. The researchers found that nearly 40 percent of the patients who did not receive the white blood cell booster early in treatment developed the fever and low white blood cell levels called febrile neutropenia, compared to only 22 percent of the patients who took the drug in conjunction with their chemotherapy, Kuderer said.

While white blood cell boosters were known to help patients receiving very intense doses of chemotherapy, this study showed that the drugs are also a benefit to cancer patients receiving more common chemotherapy doses, Kuderer said.

Recently revised American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Center Network (NCCN) guidelines for the use of drugs such as Neulasta and Neupogen align with the conclusions reached by this study.

“The new guidelines recommend using these types of drugs when at-risk patients begin chemotherapy, rather than waiting for complications to develop,” said Jeffrey Crawford, M.D., chief of the division of medical oncology at Duke and one of the study’s investigators. “The new recommendations also suggest that we need better methods to identify patients who are at higher risk of developing febrile neutropenia, and future studies will be aimed at doing just that.”

White blood cell boosters can have side effects, including bone pain, which need to be reviewed and discussed with each patient, Crawford said.

Other investigators on the study include Gary Lyman of Duke and David Dale of the University of Washington.

Duke University Medical Center (2007, July 26). White Blood Cell Booster May Help Cancer Patients Avoid Deadly Complications. ScienceDaily. Retrieved December 4, 2007, from http://www.sciencedaily.com­ /releases/2007/07/070725110020.htm

ScienceDaily (Apr. 25, 2008) — Just as fire engines arrive quickly at the scene to save people and property, the cells that fight viruses have to reach the site of an infection promptly to mount a protective response.

According to recent studies by University of Washington (UW) scientists, specialized types of white blood cells, a category called regulatory T cells, seem to help orchestrate this timely reaction to a virus invasion.

The Rudensky laboratory is noted for many contributions to the superhot field of regulatory T cells. These cells are important in controlling autoimmunity, a cellular self-attack that can lead to diseases like reactive arthritis. UW researchers and other scientists have shown that young mice deficient in regulatory T cells die from an aggressive form of autoimmunity that damages several organs.

Alexander Y. Rudensky, professor of immunology, noted the great clinical interest in the therapeutic potential of regulatory T cells. Evidence is growing on the role of regulatory T cells in keeping the body’s immune responses in check. Studies in lab animals suggest these cells might be harnessed to treat autoimmune diseases or reduce rejection of transplanted organs.

Researchers think that regulatory T cells might call a halt to immune responses as the body nears success in eliminating an infection. This suppression as the fight draws to an end would reduce tissue damage from robust immune responses.

But what happens early in infection? Does the immunity-suppressing function of regulatory T cells form an obstacle to organizing an attack on germs that have just invaded the body? Do regulatory T cells temporarily lose their suppression ability in reaction to viral-sensing mechanisms or other signals? In the recent Science Express study, researchers looked for a role for regulatory T cells during the start of a herpes simplex virus infection in mucus membranes.

When regulatory T cells are deficient in mice, the herpes simplex virus replicates rapidly in the mucus membranes and spreads to the spinal cord. Upon closer examination of these mice that lack regulatory T cells, the researchers found very little interferon, an anti-viral chemical that also boosts the immune response, at the infection site, even though it was found in the draining lymph nodes.

Also in the lymph nodes they noticed a sharp increase in certain chemokines, chemicals that stimulate immune cells to move in and cause inflammation. The presence of chemokines appeared to encourage the entry and retention of certain infection-fighting cells in the lymph nodes draining the site of infection, an ineffective place for the infection-fighting cells to be during the start of a viral attack.

The researchers also noticed a delay in killer cells, dendritic cells (the cells that capture and present foreign proteins to other immune cells), and T cells arriving at the site of infection, where they were supposed to go earlier to fulfill their virus-fighting roles. The researchers suggested that a possible reason for this tardiness is an alteration in the chemical cues necessary for these cells to migrate to the site of infection.

The authors described the finding of an immune-response promoting role for regulatory T cells during the early stages of a local infection as “unexpected,” considering the cells’ suppressor roles during later stages of an immune response.

Findings appear in the April 24 edition of Science Express. The authors of the study, “Coordination of Early Protective Immunity to Viral Infections by Regulatory T Cells,” are Jennifer M. Lund, senior fellow in immunology; Lianne Hsing, immunology graduate student; Thuy T. Pham, senior biology major; and Alexander Y. Rudensky, professor of immunology.

Adapted from materials provided by University of Washington, via EurekAlert!, a service

University of Washington (2008, April 25). Specialized White Blood Cells Coordinate First Responders To Viral Infection. ScienceDaily. Retrieved April 25, 2008, from http://www.sciencedaily.com­ /releases/2008/04/080424152249.htm

ScienceDaily (Jul. 26, 2007) — Cancer patients who receive a drug that stimulates the growth of infection-fighting white blood cells may be significantly less likely to die from a chemotherapy-related complication characterized by fever and low white blood cell levels, according to a multi-institutional study led by researchers from the University of Rochester School of Medicine and Dentistry and the Duke Comprehensive Cancer Center.

“Chemotherapy drugs target cancer cells, but they can affect healthy cells as well, including infection-fighting white blood cells,” said Nicole M. Kuderer, M.D., a hematology-oncology fellow at Duke and lead author on the publication. “When patients’ white blood cell counts drop too low, they are at risk for dangerous infections that can cause death.”

Often, chemotherapy must be delayed, reduced in strength or halted when a patient’s white blood cell count is too low, potentially leading to poorer outcomes, she added.

“Patients taking a drug known as granulocyte colony-stimulating factor early in their chemotherapy were about half as likely to develop dangerously low white blood cell counts with fever, and half as likely to die from infection,” Kuderer said. “This study represents an important part of the effort to better treat this common complication in cancer patients receiving chemotherapy.”

The researchers published their findings in the July 20, 2007 issue of the Journal of Clinical Oncology. The work was part of research being conducted by the Awareness of Neutropenia in Chemotherapy (ANC) Study Group, a multi-institution, university-based network of investigators whose work is unrestrictedly funded by Amgen, the maker of a commonly utilized white blood cell booster that goes by the names Neupogen and Neulasta. Kuderer also receives funding from the National Institutes of Health.

This study compiled the results of 17 trials involving more than 3,000 patients receiving chemotherapy of varying intensity to treat several different types of cancers. The researchers found that nearly 40 percent of the patients who did not receive the white blood cell booster early in treatment developed the fever and low white blood cell levels called febrile neutropenia, compared to only 22 percent of the patients who took the drug in conjunction with their chemotherapy, Kuderer said.

While white blood cell boosters were known to help patients receiving very intense doses of chemotherapy, this study showed that the drugs are also a benefit to cancer patients receiving more common chemotherapy doses, Kuderer said.

Recently revised American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Center Network (NCCN) guidelines for the use of drugs such as Neulasta and Neupogen align with the conclusions reached by this study.

“The new guidelines recommend using these types of drugs when at-risk patients begin chemotherapy, rather than waiting for complications to develop,” said Jeffrey Crawford, M.D., chief of the division of medical oncology at Duke and one of the study’s investigators. “The new recommendations also suggest that we need better methods to identify patients who are at higher risk of developing febrile neutropenia, and future studies will be aimed at doing just that.”

White blood cell boosters can have side effects, including bone pain, which need to be reviewed and discussed with each patient, Crawford said.

Other investigators on the study include Gary Lyman of Duke and David Dale of the University of Washington.

Duke University Medical Center (2007, July 26). White Blood Cell Booster May Help Cancer Patients Avoid Deadly Complications. ScienceDaily. Retrieved December 4, 2007, from http://www.sciencedaily.com­ /releases/2007/07/070725110020.htm