Generation Of Highly Cytotoxic Natural Killer Cells For Treatment Of Acute Myelogenous Leukemia Using A Feeder-Free, Particle-Based Approach

Keywords

AML; NK cell expansion; NK cells

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.

Publication Date

4-1-2015

Publication Title

Biology of Blood and Marrow Transplantation

Volume

21

Issue

4

Number of Pages

632-639

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bbmt.2014.12.037

Socpus ID

84924258678 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84924258678

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