Generation of highly cytotoxic natural killer cells for treatment of acute myelogenous leukemia using a feeder-free, particle-based approach

Jeremiah L. Oyer, Robert Y. Igarashi, Alexander R. Kulikowski, Dominic A. Colosimo, Melhem M. Solh, Ahmed Zakari, Yasser Khaled, Deborah A. Altomare, Alicja J. Copik

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Natural killer (NK) cell immunotherapy as a cancer treatment shows promise, but expanding NK cells consistently from a small fraction (~5%) of peripheral blood mononuclear cells (PBMCs) to therapeutic amounts remains challenging. Most current exvivo expansion methods use co-culture with feeder cells (FC), but their use poses challenges for wide clinical application. We developed a particle-based NK cell expansion technology that uses plasma membrane particles (PM-particles) derived from K562-mbIL15-41BBL FCs. These PM-particles induce selective expansion of NK cells from unsorted PBMCs, with NK cells increasing 250-fold (median, 35; 10 donors; range, 94 to 1492) after 14 days of culture and up to 1265-fold (n= 14; range, 280 to 4426) typically after 17 days. The rate and efficiency of NK cell expansions with PM-particles and live FCs are comparable and far better than stimulation with soluble 41BBL, IL-15, and IL-2. Furthermore, NK cells expand selectively with PM-particles to 86% (median, 35; range, 71% to 99%) of total cells after 14 days. The extent of NK cell expansion and cell content was PM-particle concentration dependent. These NK cells were highly cytotoxic against several leukemic cell lines and also against patient acute myelogenous leukemia blasts. Phenotype analysis of these PM-particle-expanded NK cells was consistent with an activated cytotoxic phenotype. This novel NK cell expansion methodology has promising clinical therapeutic implications.

Original languageEnglish (US)
Pages (from-to)632-639
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2015

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Acute Myeloid Leukemia
Natural Killer Cells
Cell Membrane
Therapeutics
Blood Cells
Feeder Cells
Phenotype
Interleukin-15
Coculture Techniques
Immunotherapy
Interleukin-2
Tissue Donors
Technology
Cell Line

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Generation of highly cytotoxic natural killer cells for treatment of acute myelogenous leukemia using a feeder-free, particle-based approach. / Oyer, Jeremiah L.; Igarashi, Robert Y.; Kulikowski, Alexander R.; Colosimo, Dominic A.; Solh, Melhem M.; Zakari, Ahmed; Khaled, Yasser; Altomare, Deborah A.; Copik, Alicja J.

In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 4, 01.04.2015, p. 632-639.

Research output: Contribution to journalArticle

Oyer, Jeremiah L. ; Igarashi, Robert Y. ; Kulikowski, Alexander R. ; Colosimo, Dominic A. ; Solh, Melhem M. ; Zakari, Ahmed ; Khaled, Yasser ; Altomare, Deborah A. ; Copik, Alicja J. / Generation of highly cytotoxic natural killer cells for treatment of acute myelogenous leukemia using a feeder-free, particle-based approach. In: Biology of Blood and Marrow Transplantation. 2015 ; Vol. 21, No. 4. pp. 632-639.
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