Researchers at Children's
Hospital Los Angeles have shown that a select team of immune-system
cells from patients with leukemia can be multiplied in the lab, creating
an army of natural killer cells that can be used to destroy the cancer
cells. Results of their in vitro study, published August 19 in the
could one day provide a less toxic and more effective way to battle
this cancer in children.
Leukemia cell coated with antibody is marked for destruction by activated natural killer cells (Photo: Business Wire)
Acute lymphoblastic leukemia (ALL) is the most common cancer of
childhood. This disease hinders the development of healthy blood cells
while cancer cells proliferate. Currently, children with ALL receive
chemotherapy for two to three years, exposing them to significant side
effects including changes in normal development and future fertility.
As a way to avoid these adverse effects, investigators have been
researching how to supercharge the body's innate cancer-fighting ability
- a technique called immunotherapy. One branch of the immune system -
and a possible component of immunotherapy - includes a class of cells
called natural killer (NK) cells. These specialized white blood cells
police the body and destroy abnormal cells before they turn cancerous.
Using NK cells as immunotherapy presents challenges. If the cells come
from a donor, the patient might reject the cells or wore, be at risk
for graft-versus-host disease - where contaminating donor cells regard
the patient's body as foreign and attack it. To avoid these problems,
the researchers wondered if they could enlist the help of the patients'
own, or autologous, NK cells. Using autologous cells would remove the
risks associated with donor cells.
But using autologous cells raised other issues. Would it be possible to
multiply NK cells from patients with leukemia, even though they had very
few to start with? Also, could the patient's own NK cells attack their
leukemia… and win?
"In this study, we used NK cells and ALL cells from the same pediatric
patients. We found that autologous natural killer cells will destroy the
patient's leukemia cells," said Nora
Heisterkamp, PhD, of The
Saban Research Institute of Children's Hospital Los Angeles and one
of the co-lead investigators.
To help the NK cells identify their target as leukemia cells, the
researchers also added a monoclonal antibody. Antibodies are normally
made by cells of the immune system to identify and neutralize foreign
material. Researchers can design and produce antibodies, called
monoclonal antibodies (mAb), that specifically target a certain protein
like the ones found on cancer cells. In a previous paper, Heisterkamp
showed that a mAb targeted to a specific receptor (BAFF-R) on the
leukemia cells stimulated the NK cells to attack and kill the cancer.
The BAFF-R mAb was also used in this study.
"These results are very promising - with potential as a part of first
line therapy and also as a treatment for eliminating any remaining
cancer cells, known as minimal residual disease, following standard
chemotherapy," said Hisham
Abdel-Azim, MD, of Children's Hospital Los Angeles and co-lead
investigator on the study. "We anticipate additional pre-clinical
testing and then, a clinical trial to evaluate the therapy in children
Additional contributors include first author Fei Fei, Min Lim, Aswathi
A. George, Jonathan Kirzner, Robert Seeger, and John Groffen of
Children's Hospital Los Angeles; and Dean Lee of MD Anderson Cancer
Center, Houston TX.
Funding for the study was provided in part by grants from Alex's
Lemonade Stand Foundation, the Leukemia & Lymphoma Society, the
V-Foundation and Public Health Service grant CA090321.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's
hospital on the West Coast and among the top five in the nation for
clinical excellence with its selection to the prestigious U.S. News &
World Report Honor Roll. Children's Hospital is home to The Saban
Research Institute, one of the largest and most productive pediatric
research facilities in the United States. Children's Hospital is also
one of America's premier teaching hospitals through its affiliation
since 1932 with the Keck School of Medicine of the University of
For more information, visit CHLA.org
and follow us on ResearCHLAblog.org.
Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20140820006237/en/
[ Back To NFVZone's Homepage ]