Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of...

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Autores principales:	Elisa C. Toffoli, Abdolkarim Sheikhi, Roeland Lameris, Lisa A. King, Amanda van Vliet, Bruce Walcheck, Henk M. W. Verheul, Jan Spanholtz, Jurriaan Tuynman, Tanja D. de Gruijl, Hans J. van der Vliet
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NK cells single domain antibodies bispecific VHH EGFR CD16 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1660bc09e044423aabcf4544536051f8
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spelling	oai:doaj.org-article:1660bc09e044423aabcf4544536051f82021-11-11T15:32:51ZEnhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor10.3390/cancers132154462072-6694https://doaj.org/article/1660bc09e044423aabcf4544536051f82021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5446https://doaj.org/toc/2072-6694The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.Elisa C. ToffoliAbdolkarim SheikhiRoeland LamerisLisa A. KingAmanda van VlietBruce WalcheckHenk M. W. VerheulJan SpanholtzJurriaan TuynmanTanja D. de GruijlHans J. van der VlietMDPI AGarticleNK cellssingle domain antibodiesbispecific VHHEGFRCD16Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5446, p 5446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NK cells single domain antibodies bispecific VHH EGFR CD16 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	NK cells single domain antibodies bispecific VHH EGFR CD16 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Elisa C. Toffoli Abdolkarim Sheikhi Roeland Lameris Lisa A. King Amanda van Vliet Bruce Walcheck Henk M. W. Verheul Jan Spanholtz Jurriaan Tuynman Tanja D. de Gruijl Hans J. van der Vliet Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
description	The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.
format	article
author	Elisa C. Toffoli Abdolkarim Sheikhi Roeland Lameris Lisa A. King Amanda van Vliet Bruce Walcheck Henk M. W. Verheul Jan Spanholtz Jurriaan Tuynman Tanja D. de Gruijl Hans J. van der Vliet
author_facet	Elisa C. Toffoli Abdolkarim Sheikhi Roeland Lameris Lisa A. King Amanda van Vliet Bruce Walcheck Henk M. W. Verheul Jan Spanholtz Jurriaan Tuynman Tanja D. de Gruijl Hans J. van der Vliet
author_sort	Elisa C. Toffoli
title	Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
title_short	Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
title_full	Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
title_fullStr	Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
title_full_unstemmed	Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor
title_sort	enhancement of nk cell antitumor effector functions using a bispecific single domain antibody targeting cd16 and the epidermal growth factor receptor
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1660bc09e044423aabcf4544536051f8
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Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor

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