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      Bioinspired Preservation of Natural Killer Cells for Cancer Immunotherapy

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          Abstract

          The ability to cryopreserve natural killer (NK) cells has a significant potential in modern cancer immunotherapy. Current cryopreservation protocols cause deterioration in NK cell viability and functionality. This work reports the preservation of human cytokine‐activated NK cell viability and function following cryopreservation using a cocktail of biocompatible bioinspired cryoprotectants (i.e., dextran and carboxylated ε‐poly‐L‐lysine). Results demonstrate that the recovered NK cells after cryopreservation and rewarming maintain their viability immediately after thawing at a comparable level to control (dimethyl sulfoxide‐based cryopreservation). Although, their viability drops in the first day in culture compared to controls, the cells grow back to a comparable level to controls after 1 week in culture. In addition, the anti‐tumor functional activity of recovered NK cells demonstrates higher cytotoxic potency against leukemia cells compared to control. This approach presents a new direction for NK cell preservation, focusing on function and potentially enabling storage and distribution for cancer immunotherapy.

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          Most cited references20

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          The dawning era of polymer therapeutics.

          As we enter the twenty-first century, research at the interface of polymer chemistry and the biomedical sciences has given rise to the first nano-sized (5-100 nm) polymer-based pharmaceuticals, the 'polymer therapeutics'. Polymer therapeutics include rationally designed macromolecular drugs, polymer-drug and polymer-protein conjugates, polymeric micelles containing covalently bound drug, and polyplexes for DNA delivery. The successful clinical application of polymer-protein conjugates, and promising clinical results arising from trials with polymer-anticancer-drug conjugates, bode well for the future design and development of the ever more sophisticated bio-nanotechnologies that are needed to realize the full potential of the post-genomic age.
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            NK cells and cancer: you can teach innate cells new tricks.

            Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer.
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              Natural killer cell memory in infection, inflammation and cancer.

              Immunological memory can be defined as a quantitatively and qualitatively enhanced immune response upon rechallenge. For natural killer (NK) cells, two main types of memory exist. First, similarly to T cells and B cells, NK cells can exert immunological memory after encounters with stimuli such as haptens or viruses, resulting in the generation of antigen-specific memory NK cells. Second, NK cells can remember inflammatory cytokine milieus that imprint long-lasting non-antigen-specific NK cell effector function. The basic concepts derived from studying NK cell memory provide new insights about innate immunity and could lead to novel strategies to improve treatments for infectious diseases and cancer.
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                Author and article information

                Contributors
                utkan@stanford.edu
                Journal
                Adv Sci (Weinh)
                Adv Sci (Weinh)
                10.1002/(ISSN)2198-3844
                ADVS
                Advanced Science
                John Wiley and Sons Inc. (Hoboken )
                2198-3844
                27 January 2019
                20 March 2019
                : 6
                : 6 ( doiID: 10.1002/advs.v6.6 )
                : 1802045
                Affiliations
                [ 1 ] Bio‐Acoustic‐MEMS in Medicine (BAMM) Laboratories Canary Center at Stanford for Cancer Early Detection Department of Radiology Stanford University School of Medicine Palo Alto CA 94304 USA
                [ 2 ] Molecular Imaging Program at Stanford (MIPS) Department of Radiology Stanford University School of Medicine Palo Alto CA 94304 USA
                [ 3 ] Akron Biotechnology, LLC Boca Raton FL 33487 USA
                [ 4 ] Department of Industrial and Physical Pharmacy College of Pharmacy Purdue University West Lafayette IN 47907 USA
                [ 5 ] Department of Biomedical Engineering Tufts University School of Engineering Medford MA 02155 USA
                [ 6 ] Department of Electrical Engineering (by courtesy) Stanford University School of Engineering Palo Alto CA 94304 USA
                Author notes
                [*] [* ]E‐mail: utkan@ 123456stanford.edu
                Author information
                https://orcid.org/0000-0003-3229-8596
                Article
                ADVS932
                10.1002/advs.201802045
                6425501
                e3ca702f-e062-45da-b267-8e4f6203817c
                © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2018
                Page count
                Figures: 4, Tables: 0, Pages: 7, Words: 5515
                Funding
                Funded by: National Institutes of Health
                Award ID: R01EB015776
                Funded by: Department of Defense
                Award ID: SBIR W81XWH‐15‐C‐0114
                Categories
                Communication
                Communications
                Custom metadata
                2.0
                advs932
                March 20, 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:20.03.2019

                bioinspired materials,biopreservation,cryoprotectants,immunotherapy,natural killer cells

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