Genetically modified natural killer immune cells attack and kill leukemic cells

[Guest guest]

Although this research was conducted for children with ALL, it

mentions CD19. Read on.

Ann

Genetically modified natural killer immune cells attack and kill

leukemic 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, according to St. Jude researchers.

The breakthrough suggests a way to improve the outcome of children

who receive treatment for acute lymphoblastic leukemia (ALL) or other

blood cancers. A report on this work appears in the pre-publication

online issue of Blood.

Until now, 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 antileukemic activity, according to

Dario Campana, MD, PhD, of Hematology-Oncology and Pathology and

senior author of the report.

The St. Jude researchers placed a sample of blood containing various

types of immune cells into a dish containing a type of human leukemia

cell called K562, which the team had genetically modified so the

cells carried on their surfaces many copies of two different

proteins, 4-1BBL and IL-15. These modified K562 cells quickly

stimulated the expansion of the NK cell population to more than

10,000 times their original number.

The researchers then genetically modified the growing NK cells so

they carried on their surface an artificial receptor 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.

" A potential clinical application for the technology developed in

this study is in patients with leukemia who are treated with

hematopoietic (blood-cell-forming) cell transplantation, " Campana

said. " 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. "

Chihaya Imai, MD, was the postdoctoral fellow who did most of the

work on this project; the other author of this study is Shotaro

Iwamoto, MD. Both are of Hematology-Oncology.