Credit: Bjorn Onfelt/Dan Davis
In vitro experiments suggest a patient’s own natural killer (NK) cells can be expanded and modified to fight acute lymphoblastic leukemia (ALL).
Researchers successfully expanded CD56+ cells isolated from the bone marrow and peripheral blood of ALL patients.
And these cells exhibited cytotoxicity against the patients’ own ALL cells. The effect was enhanced by the addition of IL-15 and a monoclonal antibody (mAb) targeting BAFF-R.
Hisham Abdel-Azim, MD, of Children’s Hospital Los Angeles, and his colleagues reported these results in Leukemia.
The researchers first used flow cytometry to detect CD56+ cells in bone marrow and peripheral blood samples from ALL patients. The team discovered these cells were detectable at diagnosis, post-induction, and relapse.
To expand the cells, the researchers cocultured them with artificial antigen-presenting K562 clone 9.mbIL-21 cells. The expanded CD56+ cells demonstrated allogeneic cytotoxicity against ALL cells, even in the absence of antibody.
The addition of a mAb targeting BAFF-R enhanced CD56+ cells’ cytotoxicity against ALL cells. The activity of these CD56+ cells was comparable to that of NK cells derived from healthy patients.
The researchers also compared CD56+CD3- cells to CD56+CD3+ cells and found the CD3- cells exhibited increased levels of activation in antibody-mediated cellular cytotoxicity reactions. The CD56+CD3+ cells were not stimulated by BAFF-R mAbs.
The team then tested the NK cells’ autologous cytotoxicity. And, as in previous experiments, the CD56+ cells from ALL samples demonstrated nonantibody-dependent cytotoxicity and enhanced cytotoxicity in the presence of BAFF-R mAbs.
Finally, the researchers decided to investigate whether the addition of IL-2 or IL-15 could further stimulate CD56+ cells’ cytotoxicity. And while they found that both cytokines did the job, IL-15 proved more successful.
“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 . . . following standard chemotherapy,” Dr Abdel-Azim said. “We anticipate additional preclinical testing and then a clinical trial to evaluate the therapy in children with leukemia.”
