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Biomedicines
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Recent Therapeutic Advances in Natural Killer Cells
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Recent Therapeutic Advances in Natural Killer Cells

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 23980

Special Issue Editor

Dr. Hiroshi Terunuma

E-Mail Website
Guest Editor
Tokyo Clinic, Biotherapy Institute of Japan, Tokyo, Japan
Interests: immune therapy; regenerative medicine; NK cell; dendritic cell; mesenchymal stem cell

Special Issue Information

Dear Colleagues,

Natural killer (NK) cells are classified as group I innate lymphocytes and respond quickly to a wide variety of pathological challenges. NK cells kill virally infected cells, and also detect and eliminate transformed cells at an early phase of cancer development.

NK cells were first noticed for their ability to kill tumor cells without any priming or prior activation, and to secrete cytokines such as IFN-γ, by which other immune cells like macrophages and dendritic cells are activated to induce antigen-specific cytotoxic T cells.

The NK cell-surface phenotype varies between individuals due to the MHC class I haplotypes and the combination of NK cell inhibitory or activating receptors. The number of NK cells in the body and their cytotoxic activity change with age. The ability of NK cells to remember pathogens is termed “trained immunity”.

While antigen-specific T cell therapies have been studied extensively, NK cells are also an attractive target for immunotherapies against cancer and viral infection. Researchers have developed NK cell therapies that utilize their robust cytotoxic activity to kill tumor cells and virally infected cells.

This Special Issue will focus on the potential of NK cell therapies against cancer and viral infection.

Dr. Hiroshi Terunuma
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NK cells
  • innate immunity
  • trained immunity
  • cancer immunotherapy
  • viral immunotherapy

Published Papers (5 papers)

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Research

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20 pages, 3649 KiB  
Article
Tumor Marker B7-H6 Bound to the Coiled Coil Peptide-Polymer Conjugate Enables Targeted Therapy by Activating Human Natural Killer Cells
by Barbora Kalousková, Ondřej Skořepa, Denis Cmunt, Celeste Abreu, Kateřina Krejčová, Jan Bláha, Irena Sieglová, Vlastimil Král, Milan Fábry, Robert Pola, Michal Pechar and Ondřej Vaněk
Biomedicines 2021, 9(11), 1597; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111597 - 02 Nov 2021
Cited by 2 | Viewed by 2507
Abstract
Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe the preparation [...] Read more.
Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe the preparation of pHPMA-based copolymer conjugated with immunologically active protein B7-H6 via complementary coiled coil VAALEKE (peptide E) and VAALKEK (peptide K) sequences. Receptor B7-H6 was described as a binding partner of NKp30, and its expression has been proven for various tumor cell lines. The binding of B7-H6 to NKp30 activates NK cells and results in Fas ligand or granzyme-mediated apoptosis of target tumor cells. In this work, we optimized the expression of coiled coil tagged B7-H6, its ability to bind activating receptor NKp30 has been confirmed by isothermal titration calorimetry, and the binding stoichiometry of prepared chimeric biopolymer has been characterized by analytical ultracentrifugation. Furthermore, this coiled coil B7-H6-loaded polymer conjugate activates NK cells in vitro and, in combination with coiled coil scFv, enables their targeting towards a model tumor cell line. Prepared chimeric biopolymer represents a promising precursor for targeted cancer immunotherapy by activating the cytotoxic activity of natural killer cells. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Natural Killer Cells)
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Review

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20 pages, 1513 KiB  
Review
Exploring the Utility of NK Cells in COVID-19
by Xuewen Deng, Hiroshi Terunuma and Mie Nieda
Biomedicines 2022, 10(5), 1002; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051002 - 26 Apr 2022
Cited by 11 | Viewed by 3860
Abstract
Coronavirus disease 2019 (COVID-19) can manifest as acute respiratory distress syndrome and is associated with substantial morbidity and mortality. Extensive data now indicate that immune responses to SARS-CoV-2 infection determine the COVID-19 disease course. A wide range of immunomodulatory agents have been tested [...] Read more.
Coronavirus disease 2019 (COVID-19) can manifest as acute respiratory distress syndrome and is associated with substantial morbidity and mortality. Extensive data now indicate that immune responses to SARS-CoV-2 infection determine the COVID-19 disease course. A wide range of immunomodulatory agents have been tested for the treatment of COVID-19. Natural killer (NK) cells play an important role in antiviral innate immunity, and anti-SARS-CoV-2 activity and antifibrotic activity are particularly critical for COVID-19 control. Notably, SARS-CoV-2 clearance rate, antibody response, and disease progression in COVID-19 correlate with NK cell status, and NK cell dysfunction is linked with increased SARS-CoV-2 susceptibility. Thus, NK cells function as the key element in the switch from effective to harmful immune responses in COVID-19. However, dysregulation of NK cells has been observed in COVID-19 patients, exhibiting depletion and dysfunction, which correlate with COVID-19 severity; this dysregulation perhaps contributes to disease progression. Given these findings, NK-cell-based therapies with anti-SARS-CoV-2 activity, antifibrotic activity, and strong safety profiles for cancers may encourage the rapid application of functional NK cells as a potential therapeutic strategy to eliminate SARS-CoV-2-infected cells at an early stage, facilitate immune–immune cell interactions, and favor inflammatory processes that prevent and/or reverse over-inflammation and inhibit fibrosis progression, thereby helping in the fight against COVID-19. However, our understanding of the role of NK cells in COVID-19 remains incomplete, and further research on the involvement of NK cells in the pathogenesis of COVID-19 is needed. The rationale of NK-cell-based therapies for COVID-19 has to be based on the timing of therapeutic interventions and disease severity, which may be determined by the balance between beneficial antiviral and potential detrimental pathologic actions. NK cells would be more effective early in SARS-CoV-2 infection and prevent the progression of COVID-19. Immunomodulation by NK cells towards regulatory functions could be useful as an adjunct therapy to prevent the progression of COVID-19. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Natural Killer Cells)
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16 pages, 334 KiB  
Review
New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology
by Mehmet Gunduz, Pinar Ataca Atilla and Erden Atilla
Biomedicines 2021, 9(9), 1201; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091201 - 11 Sep 2021
Cited by 4 | Viewed by 2412
Abstract
NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challenges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly [...] Read more.
NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challenges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technological advancements in gene delivery, gene editing and chimeric antigen receptors (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable “off-the-shelf” products with fewer side effects. In this review, we highlight recent advances in NK cell biology along with current approaches for potentiating NK cell proliferation and activity, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Natural Killer Cells)
16 pages, 621 KiB  
Review
Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging
by Xuewen Deng, Hiroshi Terunuma and Mie Nieda
Biomedicines 2021, 9(5), 557; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050557 - 17 May 2021
Cited by 6 | Viewed by 4204
Abstract
Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell [...] Read more.
Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Natural Killer Cells)
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13 pages, 1355 KiB  
Review
Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections
by Ekaterina Zmievskaya, Aygul Valiullina, Irina Ganeeva, Alexey Petukhov, Albert Rizvanov and Emil Bulatov
Biomedicines 2021, 9(1), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9010059 - 09 Jan 2021
Cited by 58 | Viewed by 9677
Abstract
Adoptive cell transfer (ACT) has long been at the forefront of the battle with cancer that began last century with the therapeutic application of tumor-infiltrating lymphocytes (TILs) against melanoma. The development of novel ACT approaches led researchers and clinicians to highly efficient technologies [...] Read more.
Adoptive cell transfer (ACT) has long been at the forefront of the battle with cancer that began last century with the therapeutic application of tumor-infiltrating lymphocytes (TILs) against melanoma. The development of novel ACT approaches led researchers and clinicians to highly efficient technologies based on genetically engineered T lymphocytes, with chimeric antigen receptor (CAR)-T cells as the most prominent example. CARs consist of an extracellular domain that represents the single-chain variable fragment (scFv) of a monoclonal antibody (mAb) responsible for target recognition and the intracellular domain, which was built from up to several signaling motifs that mediated T cell activation. The number of potential targets amenable for CAR-T cell therapy is expanding rapidly, which means that the tremendous success of this approach in oncology could be further translated to treating other diseases. In this review, we outlined modern trends and recent developments in CAR-T cell therapy from an unusual point of view by focusing on diseases beyond cancer, such as autoimmune disorders and viral infections, including SARS-CoV-2. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Natural Killer Cells)
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