Korean J Lab Med 2009; 29(2): 89-96

Published online April 1, 2009

Copyright © Korean Society for Laboratory Medicine.

Expansion and Activation of Natural Killer Cells for Cancer Immunotherapy

Duck Cho, M.D.1 and Dario Campana, M.D.1,2

Departments of Oncology1 and Pathology2, St. Jude Children’s Research Hospital, Memphis, TN, USA

Correspondence to: Dario Campana, M.D., Ph.D.
Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
Tel : +901-4595 2528, Fax : +901-4595 5947
E-mail :

*This work was supported by grants CA113482 and CA21765 from the National Cancer Institute, grants from the Assisi Foundation and from the Fondation de Gouverneurs de l’Espoir, and by the American Lebanese Syrian Associated Charities (ALSAC).

Received: February 18, 2009; Revised: March 25, 2009; Accepted: March 27, 2009


Natural killer (NK) cells can kill a wide range of cancer cells and are a promising tool for cell therapy of cancer. NK cells cytotoxicity is regulated by a balance between stimulatory and inhibitory signals. Interleukin-2 is known to increase NK cell cytotoxicity. Although many cytokines have been studied in efforts to induce durable NK cell expansions, most reports indicate a rather modest effect and the requirement for additional stimuli. We found that contact with the K562 myeloid leukemia cell line, genetically modified to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB, induced vigorous expansion of NK cells from peripheral blood. Based on these findings, we developed a method for large-scale clinical-grade expansion of NK cells. This method is currently used to expand allogeneic NK cells for infusion in patients with leukemia and solid tumors. We here summarize methods for expansion and activation of NK cells from human peripheral blood mononuclear cells as well as clinical-scale methods to produce NK cells for immunotherapy under Current Good Manufacturing Practices (cGMP) conditions.

Keywords: NK cells, Cell therapy, Acute myeloid leukemia, Acute lymphoblastic leukemia, Chimeric