St Jude lab studies shows that new genetic modification and culture techniques produce NK cells with significantly
enhanced ability to eradicate leukemia cells -
Natural killer (NK) immune system cells can be genetically modified to brandish a powerful "on-switch" that prompts them to
aggressively attack and kill leukemic cells. This finding, from researchers at St. Jude Children's Research Hospital,
suggests a way to improve the outcome of children who receive treatment for acute lymphoblastic leukemia (ALL) or other blood
cancers.
Results of the St. Jude study are published in the current online issue of Blood.
The researchers demonstrated how to overcome significant technical hurdles that have until now slowed development of NK-based
therapies for ALL, according to Dario Campana, M.D., Ph.D., a member of St. Jude Hematology-Oncology and Pathology, and
senior author of the Blood report. Progress in adapting NK cells to the treatment of ALL had been significantly hampered
because researchers were not able to grow large numbers of these immune cells in the laboratory, and because NK cells
normally have only weak anti-leukemic activity.
The key breakthroughs made by the St. Jude team were the development of a laboratory technique for rapidly producing a large,
pure population of NK cells from a small sample of blood; and developing a technique for genetically modifying NK cells so
that they would become potent killers when they encountered leukemic cells.
In order to grow large populations of NK cells, the team started with samples of blood containing a variety of different
immune system cells. They placed this sample into a dish containing a type of human leukemia cell called K562. Campana's team
genetically modified the K562 cells so they carried on their surfaces many copies of two different proteins, 4-1BBL and
IL-15. The genetically modified K562 cells quickly stimulated the expansion of the NK cell population to more than10,000
times their original number. The technique triggered growth of NK cells specifically, which greatly simplified the ability of
the researchers to collect a pure population of these immune cells.
The researchers then genetically modified the growing NK cells so they carried on their surface an artificial receptor that
made them particularly aggressive and effective killers that attacked only leukemic cells. A receptor is a protein that binds
to a specific target molecule. The artificial receptor on the NK molecule was designed to recognize a protein called CD19,
which is found on the surface of leukemic cells. When the receptor bound to CD19 on leukemic cells, it set off a reaction
that super-charged the killing activity of the NK cell.
"By developing a technique for cultivating large numbers of NK cells from a small blood sample, we made it practical to
consider them a potential treatment against many different types of cancer," Campana said. "By genetically modifying NK cells
so they expressed the CD19 receptor, we made them specifically effective against ALL cells."
A potential clinical application for the technology developed in this study is in leukemia patients who are treated with
hematopoietic (blood cell-forming) cell transplantation. In this case, NK cells will be derived from the transplant donor,
expanded and genetically modified. These modified NK cells will then be infused into the patient after the transplant in
order to eliminate residual leukemic cells. In another application, NK cells could be obtained from a patient while in
remission and then reinfused after genetic modification if the patient suffers a resurgence of the leukemia.
"We look forward to seeing this strategy being added to the management of children with ALL," said Chihaya Imai, M.D., the
postdoctoral student who did most of the work on this project.
The other author of this study is Shotaro Iwamoto, M.D., of St. Jude.
This work was supported in part by the National Cancer Institute and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving
children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn.,
St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for
treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported
by ALSAC, its fundraising organization. For more information, please visit stjude.
Contact: Bonnie Cameron
bonniemeronstjude
901-495-4815
St. Jude Children's Research Hospital
stjude