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Cells
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Natural Killer Cells in Cancer Immunotherapy
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Natural Killer Cells in Cancer Immunotherapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 3282

Special Issue Editor

Prof. Dr. Vladimir Jurisic

E-Mail Website
Guest Editor
Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
Interests: innate immunity; NK cells; cytokines; immunomodulation; oncology; hematology; biochemistry; tumor markers; molecular markers; polymorphisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since the discovery and first description of NK cells, a special population of peripheral blood lymphocytes, these cells have been of great scientific interest. NK cells were first described as large granular lymphocytes with a specific morphology and role in oncology. Today, with the help of multicolor flow cytometry, the focus of global research is the examination of markers responsible for the activation and inhibition of NK cells as well as gene regulation in the light of understanding tumor suppression in oncology patients. Based on this, this Special Issue will discuss and analyze NK cell research as well as the clinical possibility of NK cell immunomodulation. We hope that such research and original results provide new breakthroughs in the treatment of malignant diseases, as understanding all the complex processes and principles of immunology can be of great importance in clinical practice.

Prof. Dr. Vladimir Jurisic
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. Cells is an international peer-reviewed open access semimonthly 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 2700 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.

Published Papers (2 papers)

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Research

19 pages, 4201 KiB  
Article
NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment
by Benjamin Motais, Sandra Charvátová, Zuzana Walek, Roman Hájek and Juli R. Bagó
Cells 2023, 12(23), 2748; https://doi.org/10.3390/cells12232748 - 30 Nov 2023
Cited by 1 | Viewed by 1455
Abstract
Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) [...] Read more.
Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the piggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45.1% (±26.1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and γ-secretase inhibitors (GSIs), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrates the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy. Full article
(This article belongs to the Special Issue Natural Killer Cells in Cancer Immunotherapy)
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22 pages, 4871 KiB  
Article
Reduction of Ca2+ Entry by a Specific Block of KCa3.1 Channels Optimizes Cytotoxic Activity of NK Cells against T-ALL Jurkat Cells
by Miguel Olivas-Aguirre, Laura Hadit Cruz-Aguilar, Igor Pottosin and Oxana Dobrovinskaya
Cells 2023, 12(16), 2065; https://doi.org/10.3390/cells12162065 - 15 Aug 2023
Cited by 2 | Viewed by 1205
Abstract
Degranulation mediated killing mechanism by NK cells is dependent on store-operated Ca2+ entry (SOCE) and has optimum at moderate intracellular Ca2+ elevations so that partial block of SOCE optimizes the killing process. In this study, we tested the effect of the [...] Read more.
Degranulation mediated killing mechanism by NK cells is dependent on store-operated Ca2+ entry (SOCE) and has optimum at moderate intracellular Ca2+ elevations so that partial block of SOCE optimizes the killing process. In this study, we tested the effect of the selective blocker of KCa3.1 channel NS6180 on SOCE and the killing efficiency of NK cells from healthy donors and NK-92 cells against T-ALL cell line Jurkat. Patch-clamp analysis showed that only one-quarter of resting NK cells functionally express KCa3.1 current, which increases 3-fold after activation by interleukins 15 and 2. Nevertheless, blockage of KCa3.1 significantly reduced SOCE and intracellular Ca2+ rise induced by IL-15 or target cell recognition. NS6180 (1 μM) decreased NK degranulation at zero time of coculture with Jurkat cells but already after 1 h, the degranulation reached the same level as in the control. Monitoring of target cell death by flow cytometry and confocal microscopy demonstrated that NS6180 significantly improved the killing ability of NK cells after 1 h in coculture with Jurkat cells and increased the Jurkat cell fraction with apoptotic and necrotic markers. Our data evidence a strong dependence of SOCE on KCa3.1 activity in NK cells and that KCa3.1 specific block can improve NK cytotoxicity. Full article
(This article belongs to the Special Issue Natural Killer Cells in Cancer Immunotherapy)
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