Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs
Natural killer (NK) cells hold a pivotal role in tumor-targeting monoclonal antibody (mAb)-based activity due to the expression of CD16, the low-affinity receptor for IgG. Indeed, beyond exerting cytotoxic function, activated NK cells also produce an array of cytokines and chemokines, through which...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/10/2500 |
| _version_ | 1797533341062266880 |
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| author | Cristina Capuano Chiara Pighi Simone Battella Davide De Federicis Ricciarda Galandrini Gabriella Palmieri |
| author_facet | Cristina Capuano Chiara Pighi Simone Battella Davide De Federicis Ricciarda Galandrini Gabriella Palmieri |
| author_sort | Cristina Capuano |
| collection | DOAJ |
| description | Natural killer (NK) cells hold a pivotal role in tumor-targeting monoclonal antibody (mAb)-based activity due to the expression of CD16, the low-affinity receptor for IgG. Indeed, beyond exerting cytotoxic function, activated NK cells also produce an array of cytokines and chemokines, through which they interface with and potentiate adaptive immune responses. Thus, CD16-activated NK cells can concur to mAb-dependent “vaccinal effect”, i.e., the development of antigen-specific responses, which may be highly relevant in maintaining long-term protection of treated patients. On this basis, the review will focus on strategies aimed at potentiating NK cell-mediated antitumor functions in tumor-targeting mAb-based regimens, represented by (a) mAb manipulation strategies, aimed at augmenting recruitment and efficacy of NK cells, such as Fc-engineering, and the design of bi- or trispecific NK cell engagers and (b) the possible exploitation of memory NK cells, whose distinctive characteristics (enhanced responsiveness to CD16 engagement, longevity, and intrinsic resistance to the immunosuppressive microenvironment) may maximize therapeutic mAb antitumor efficacy. |
| first_indexed | 2024-03-10T11:13:09Z |
| format | Article |
| id | doaj.art-5177b49c2c2f40dfa57e145d54396c24 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:13:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5177b49c2c2f40dfa57e145d54396c242023-11-21T20:35:28ZengMDPI AGCancers2072-66942021-05-011310250010.3390/cancers13102500Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbsCristina Capuano0Chiara Pighi1Simone Battella2Davide De Federicis3Ricciarda Galandrini4Gabriella Palmieri5Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyNatural killer (NK) cells hold a pivotal role in tumor-targeting monoclonal antibody (mAb)-based activity due to the expression of CD16, the low-affinity receptor for IgG. Indeed, beyond exerting cytotoxic function, activated NK cells also produce an array of cytokines and chemokines, through which they interface with and potentiate adaptive immune responses. Thus, CD16-activated NK cells can concur to mAb-dependent “vaccinal effect”, i.e., the development of antigen-specific responses, which may be highly relevant in maintaining long-term protection of treated patients. On this basis, the review will focus on strategies aimed at potentiating NK cell-mediated antitumor functions in tumor-targeting mAb-based regimens, represented by (a) mAb manipulation strategies, aimed at augmenting recruitment and efficacy of NK cells, such as Fc-engineering, and the design of bi- or trispecific NK cell engagers and (b) the possible exploitation of memory NK cells, whose distinctive characteristics (enhanced responsiveness to CD16 engagement, longevity, and intrinsic resistance to the immunosuppressive microenvironment) may maximize therapeutic mAb antitumor efficacy.https://www.mdpi.com/2072-6694/13/10/2500tumor-targeting mAbmemory NK cellsvaccinal effectIFNγCD16ADCC |
| spellingShingle | Cristina Capuano Chiara Pighi Simone Battella Davide De Federicis Ricciarda Galandrini Gabriella Palmieri Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs Cancers tumor-targeting mAb memory NK cells vaccinal effect IFNγ CD16 ADCC |
| title | Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs |
| title_full | Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs |
| title_fullStr | Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs |
| title_full_unstemmed | Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs |
| title_short | Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs |
| title_sort | harnessing cd16 mediated nk cell functions to enhance therapeutic efficacy of tumor targeting mabs |
| topic | tumor-targeting mAb memory NK cells vaccinal effect IFNγ CD16 ADCC |
| url | https://www.mdpi.com/2072-6694/13/10/2500 |
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