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Natural Killer Cells, the Terminator of Aggressive Tumors: Development, Function Source and Effective Therapeutics

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Special Issue Editors

Dr. Anahid Jewett

E-Mail Website1 Website2 Website3
Guest Editor

1. Tumor Immunology Laboratory, Division of Oral Biology and Medicine, School of Dentistry and Medicine, Los Angeles, CA 90095, USA
2. Division of Advanced Prosthodontics and Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA 90095, USA
3. The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA 90095, USA
Interests: natural killer cells; differentiation; cancer stem cells; cell death; NK therapeutics
Special Issues, Collections and Topics in MDPI journals

Dr. Kawaljit Kaur

E-Mail Website
Guest Editor

Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Department of Dentistry, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA
Interests: natural killer cells; oral cancer; pancreatic cancer; cancer immunotherapy; humanized-BLT mice; osteoclasts; cell expansion; T cells; osteonecrosis of jaw; probiotic bacteria; chemotherapy; bisphosphonates; monocytes; dendritic cells; clinical trials; NAC
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We have long known about the important roles of NK cells in cancer therapy; however, only recently have we started to appreciate the scope of the significance of these cells in tumor therapy. Identification of cancer stem cells or poorly differentiated tumors as prime targets of NK cells has finally shown the indispensable role of these cells in cancer therapy. In addition, successful cancer therapy will require restoration of both NK and T cell functions in cancer patients, since each are likely designed to target different subsets of tumor cells with opposing degrees of cellular differentiation with differing expression of MHC class I. NK cells mediate successful control of the tumor cells by their direct cytolytic effect and/or through antibody-mediated ADCC or indirectly through differentiation of tumor cells by IFN-g, which increases the efficacy of chemotherapeutic and radiotherapeutic targeting strategies (Fig. 1). Moreover, strategies should be designed to allow maintenance of good NK expansion and function in cancer patients, since not only are they capable of expanding cancer suppressing CD8+ T cells, but they are also key in limiting the expansion of immune suppressive cells such as TAMs, Tregs, MDSCs, MSCs, and fibroblasts. Mature allogeneic activated NK cells can be combined with other immunotherapeutic strategies such as oncolytic viruses, ADCC-inducing antibodies, check point inhibitors, CAR-T, CAR-NK, and chemotherapeutic and radiotherapeutic strategies for the ultimate goal of tumor eradication.

Dr. Anahid Jewett
Dr. Kawaljit Kaur
Guest Editors

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Keywords

cancer stem cells/poorly differentiated tumors
MHC class I
activating NK receptors
ADCC
development
NK function

Published Papers (2 papers)

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Research

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16 pages, 2721 KiB

Open AccessArticle

Bi-Specific Killer Cell Engager Enhances NK Cell Activity against Interleukin-13 Receptor Alpha-2 Positive Gliomas

by Kristen D. Pawlowski, Joseph T. Duffy, Arushi Tiwari, Markella Zannikou and Irina V. Balyasnikova

Cells 2023, 12(13), 1716; https://doi.org/10.3390/cells12131716 - 25 Jun 2023

Cited by 3 | Viewed by 2041

Abstract

Glioblastoma (GBM) is a lethal brain tumor with limited therapeutic options. Bi-specific killer cell engagers (BiKEs) are novel immunotherapies designed to engage natural killer (NK) cells against cancer. We designed a BiKE molecule consisting of a single-domain CD16 antibody, an interleukin-15 linker, and a single-chain variable antibody against the glioma-associated antigen interleukin 13 receptor alpha 2 (IL13Rα2). Recombinant BiKE protein was expressed in HEK cells and purified. Flow cytometric analysis of co-cultures of peripheral blood-derived NK cells with GBM6 and GBM39 patient-derived xenograft lines revealed significantly increased activation of NK cells (CD25+CD69+) and increased glioma cell killing following BiKE treatment compared to controls (n = 4, p < 0.01). Glioma cell killing was also confirmed via immunofluorescence staining for cleaved caspase-3 (p < 0.05). In vivo, intracranial delivery of NK cells with BiKE extended median survival in mice bearing GBM6 (p < 0.01) and GBM12 (p < 0.01) tumors compared to controls. Finally, histological analysis of brain tissues revealed a higher frequency of peritumoral NK cells in mice treated with BiKE than with NK cells alone (p < 0.05). In conclusion, we demonstrate that a BiKE generated in a mammalian expression system is functional in augmenting NK cell targeting of IL13Rα2-positive gliomas. Full article

(This article belongs to the Special Issue Natural Killer Cells, the Terminator of Aggressive Tumors: Development, Function Source and Effective Therapeutics)

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Review

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14 pages, 609 KiB

Open AccessReview

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

by Luis F. Porrata

Cells 2022, 11(21), 3469; https://doi.org/10.3390/cells11213469 - 2 Nov 2022

Cited by 1 | Viewed by 1490

Abstract

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation. Full article

(This article belongs to the Special Issue Natural Killer Cells, the Terminator of Aggressive Tumors: Development, Function Source and Effective Therapeutics)

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