Generation of Highly Cytotoxic Natural Killer Cells for Treatment of Acute Myelogenous Leukemia Using a Feeder-Free, Particle-Based Approach

    Authors

    J. L. Oyer; R. Y. Igarashi; A. R. Kulikowski; D. A. Colosimo; M. M. Solh; A. Zakari; Y. A. Khaled; D. A. Altomare;A. J. Copik

    Comments

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    Abbreviated Journal Title

    Biol. Blood Marrow Transplant.

    Keywords

    NK cells; NK cell expansion; AML; ACUTE MYELOID-LEUKEMIA; EX-VIVO EXPANSION; NK CELLS; CLINICAL-GRADE; TARGET-CELLS; LARGE-SCALE; IN-VITRO; IMMUNOTHERAPY; TRANSPLANTATION; CANCER; Hematology; Immunology; Transplantation

    Abstract

    Natural killer (NK) cell immunotherapy as a cancer treatment shows promise, but expanding NK cells consistently from a small fraction (similar to 5%) of peripheral blood mononuclear cells (PBMCs) to therapeutic amounts remains challenging. Most current ex vivo 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 NI( 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. (C) 2015 American Society for Blood and Marrow Transplantation.

    Journal Title

    Biology of Blood and Marrow Transplantation

    Volume

    21

    Issue/Number

    4

    Publication Date

    1-1-2015

    Document Type

    Article

    Language

    English

    First Page

    632

    Last Page

    639

    WOS Identifier

    WOS:000351790300009

    ISSN

    1083-8791

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