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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5446 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:05:16Z |
| format | Article |
| id | doaj.art-1660bc09e044423aabcf4544536051f8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:05:16Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1660bc09e044423aabcf4544536051f82023-11-22T20:35:23ZengMDPI AGCancers2072-66942021-10-011321544610.3390/cancers13215446Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor ReceptorElisa C. Toffoli0Abdolkarim Sheikhi1Roeland Lameris2Lisa A. King3Amanda van Vliet4Bruce Walcheck5Henk M. W. Verheul6Jan Spanholtz7Jurriaan Tuynman8Tanja D. de Gruijl9Hans J. van der Vliet10Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsGlycostem Therapeutics, 5349 AB Oss, The NetherlandsDepartment of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USARadboud Institute for Health Sciences, Department of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsGlycostem Therapeutics, 5349 AB Oss, The NetherlandsAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, 1081 HV Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsThe 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.https://www.mdpi.com/2072-6694/13/21/5446NK cellssingle domain antibodiesbispecific VHHEGFRCD16 |
| spellingShingle | 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 Cancers NK cells single domain antibodies bispecific VHH EGFR CD16 |
| title | 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_short | 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 |
| topic | NK cells single domain antibodies bispecific VHH EGFR CD16 |
| url | https://www.mdpi.com/2072-6694/13/21/5446 |
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