The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy

Gerhard Hamilton, Adelina Plangger Department of Vascular Surgery, Medical University of Vienna, Vienna, AustriaCorrespondence: Gerhard HamiltonDepartment of Vascular Surgery, Medical University of Vienna, Spitalgasse 23, Vienna, A-1090, AustriaTel +43-1-40400Email gerhard.hamilton@meduniwien.ac.atA...

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Autores principales:	Hamilton G, Plangger A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	natural killer cells immunotherapy chimeric antigen receptor antibody-dependent cytotoxicity lung cancer interleukins Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bbfd59578553413294407459f3416055
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spelling	oai:doaj.org-article:bbfd59578553413294407459f34160552021-12-02T16:40:01ZThe Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy1177-5491https://doaj.org/article/bbfd59578553413294407459f34160552021-07-01T00:00:00Zhttps://www.dovepress.com/the-impact-of-nk-cell-based-therapeutics-for-the-treatment-of-lung-can-peer-reviewed-fulltext-article-BTThttps://doaj.org/toc/1177-5491Gerhard Hamilton, Adelina Plangger Department of Vascular Surgery, Medical University of Vienna, Vienna, AustriaCorrespondence: Gerhard HamiltonDepartment of Vascular Surgery, Medical University of Vienna, Spitalgasse 23, Vienna, A-1090, AustriaTel +43-1-40400Email gerhard.hamilton@meduniwien.ac.atAbstract: Lung cancer has a dismal prognosis and novel targeted therapies leave still room for major improvements and better outcomes. Immunotherapy targeting immune checkpoint (IC) proteins, either as single agents or in combination with chemotherapy, is active but responders constitute only approximately 10– 15% of non-small cell lung cancer (NSCLC) patients. Other effector immune cells such as CAR-T cells or NK cells may help to overcome the limitations of the IC inhibitor therapies for lung cancer. NK cells can kill tumor cells without previous priming and are present in the circulatory system and lymphoid organs. Tissue-residing NK cells differ from peripheral effector cells and, in case of the lung, comprise CD56bright CD16-negative populations showing high cytokine release but low cytotoxicity in contrast to the circulating CD56dim CD16-positive NK cells exhibiting high cytotoxic efficacy. This local attenuation of NK cell killing potency seems due to a specific stage of NK differentiation, immunosuppressive factors as well as presence of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (TREGs). Improved NK cell-based immunotherapies involve IL-2-stimulated effector cells, NK cells expanded with the help of cytokines, permanent NK cell lines, induced pluripotent stem cell-derived NK cells and NK cells armed with chimeric antigen receptors. Compared to CAR T cell therapy, NK cells administration is devoid of graft-versus-host disease (GvHD) and cytokine-release syndrome. Although NK cells are clearly active against lung cancer cells, the low-cytotoxicity differentiation state in lung tumors, the presence of immunosuppressive leucocyte populations, limited infiltration and adverse conditions of the microenvironment need to be overcome. This goal may be achieved in the future using large numbers of activated and armed NK cells as provided by novel methods in NK cell isolation, expansion and stimulation of cytotoxic activity, including combinations with monoclonal antibodies in antibody-dependent cytotoxicity (ADCC). This review discusses the basic characteristics of NK cells and the potential of NK cell preparations in cancer therapy.Keywords: natural killer cells, immunotherapy, chimeric antigen receptor, antibody-dependent cytotoxicity, lung cancer, interleukinsHamilton GPlangger ADove Medical Pressarticlenatural killer cellsimmunotherapychimeric antigen receptorantibody-dependent cytotoxicitylung cancerinterleukinsMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 15, Pp 265-277 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	natural killer cells immunotherapy chimeric antigen receptor antibody-dependent cytotoxicity lung cancer interleukins Medicine (General) R5-920
spellingShingle	natural killer cells immunotherapy chimeric antigen receptor antibody-dependent cytotoxicity lung cancer interleukins Medicine (General) R5-920 Hamilton G Plangger A The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
description	Gerhard Hamilton, Adelina Plangger Department of Vascular Surgery, Medical University of Vienna, Vienna, AustriaCorrespondence: Gerhard HamiltonDepartment of Vascular Surgery, Medical University of Vienna, Spitalgasse 23, Vienna, A-1090, AustriaTel +43-1-40400Email gerhard.hamilton@meduniwien.ac.atAbstract: Lung cancer has a dismal prognosis and novel targeted therapies leave still room for major improvements and better outcomes. Immunotherapy targeting immune checkpoint (IC) proteins, either as single agents or in combination with chemotherapy, is active but responders constitute only approximately 10– 15% of non-small cell lung cancer (NSCLC) patients. Other effector immune cells such as CAR-T cells or NK cells may help to overcome the limitations of the IC inhibitor therapies for lung cancer. NK cells can kill tumor cells without previous priming and are present in the circulatory system and lymphoid organs. Tissue-residing NK cells differ from peripheral effector cells and, in case of the lung, comprise CD56bright CD16-negative populations showing high cytokine release but low cytotoxicity in contrast to the circulating CD56dim CD16-positive NK cells exhibiting high cytotoxic efficacy. This local attenuation of NK cell killing potency seems due to a specific stage of NK differentiation, immunosuppressive factors as well as presence of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (TREGs). Improved NK cell-based immunotherapies involve IL-2-stimulated effector cells, NK cells expanded with the help of cytokines, permanent NK cell lines, induced pluripotent stem cell-derived NK cells and NK cells armed with chimeric antigen receptors. Compared to CAR T cell therapy, NK cells administration is devoid of graft-versus-host disease (GvHD) and cytokine-release syndrome. Although NK cells are clearly active against lung cancer cells, the low-cytotoxicity differentiation state in lung tumors, the presence of immunosuppressive leucocyte populations, limited infiltration and adverse conditions of the microenvironment need to be overcome. This goal may be achieved in the future using large numbers of activated and armed NK cells as provided by novel methods in NK cell isolation, expansion and stimulation of cytotoxic activity, including combinations with monoclonal antibodies in antibody-dependent cytotoxicity (ADCC). This review discusses the basic characteristics of NK cells and the potential of NK cell preparations in cancer therapy.Keywords: natural killer cells, immunotherapy, chimeric antigen receptor, antibody-dependent cytotoxicity, lung cancer, interleukins
format	article
author	Hamilton G Plangger A
author_facet	Hamilton G Plangger A
author_sort	Hamilton G
title	The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
title_short	The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
title_full	The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
title_fullStr	The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
title_full_unstemmed	The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy
title_sort	impact of nk cell-based therapeutics for the treatment of lung cancer for biologics: targets and therapy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/bbfd59578553413294407459f3416055
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The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy

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