Large scale ex vivo expansion and activation of human natural killer cells for autologous therapy

Jeffrey S Miller, S. Klingsporn, J. Lund, E. H. Perry, C. Verfaillie, P. McGlave

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Immunotherapy with recombinant interleukin-2 (rIL-2) activated natural killer cells (ANK) may be useful in the treatment of malignancies. Difficulties in large scale cultivation of purified ANK have hampered clinical trials. In a first set of experiments designed to characterize ANK precursors in blood we demonstrated that both FACS purified CD56+/CD3- and CD56-/CD3- cultured with rIL-2 give rise to an expanded cell population bearing the CD56+ (bright)/CD3- phenotype and having both NK and lymphokine-activated killer (LAK) activity. Cultivation of NK was markedly enhanced by autologous monocytes. We next demonstrated that panning of peripheral blood stem cells on CD5/CD8 coated flasks yielded a starting population enriched for monocytes and NK precursors which after cultivation resulted in production of 4 x 1010 highly cytotoxic ANK adequate for in vivo clinical trails. Finally, we demonstrated that ANK generated in high dose IL-2 maintain NK and LAK activity for up to 6 days when cultured in as little as 1 U/ml rIL-2. This may allow infusion of ANK with a rIL-2 dose achievable in vivo that does not produce significant systemic toxicity. We plan to test the efficacy of ANK to prevent relapse in a minimal residual disease state following autologous bone marrow transplant.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalBone marrow transplantation
Issue number4
StatePublished - 1994


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