| DOI | Resolve DOI: https://doi.org/10.1021/acs.molpharmaceut.1c00208 |
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| Author | Search for: van Faassen, Henk1; Search for: Jo, Dong-Hyeon; Search for: Ryan, Shannon1; Search for: Lowden, Michael J.1; Search for: Raphael, Shalini1; Search for: MacKenzie, C. Roger1; Search for: Lee, Seung-Hwan; Search for: Hussack, Greg1; Search for: Henry, Kevin A.1ORCID identifier: https://orcid.org/0000-0003-0477-0558 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Funder | Search for: National Research Council of Canada |
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| Format | Text, Article |
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| Subject | single-domain antibody; VHH; nanobody; CD16; natural killer cell; bispecific NK cell engager; cancer immunotherapy |
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| Publication date | 2021-05-17 |
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| Publisher | American Chemical Society |
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| Access condition | - Multispecific antibodies that bridge immune effector and tumor cells have shown promising preclinical and clinical efficacies. Here, we isolated and characterized novel llama single-domain antibodies (sdAbs) against CD16. One sdAb, NRC-sdAb048, bound recombinant human and cynomolgus monkey CD16 ectodomains with equivalent affinity (KD: 1 nM) but did not recognize murine CD16. Binding was similar for human CD16a expressed on NK cells and CD16b (NA2) expressed on neutrophils but dramatically weaker (KD: ∼6 μM) for the CD16b (NA1) allotype. The sdAb stained primary human peripheral blood NK cells. Irrespective of fusion orientation and linker length, bispecific sdAb–sdAb and sdAb–scFv dimers (anti-CD16/EGFR, anti-CD16/HER2, and anti-CD16/CD19) retained full binding affinity for each target, coengaged both antigens simultaneously, elicited ADCC against target antigen-expressing tumor cells in a reporter bioassay, and triggered target-specific activation and degranulation of primary NK cells as measured via interferon-γ and CD107a expression. These molecules may have applications in cancer immunotherapy.
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 5bb9162d-a754-4dd8-9abd-5a2db5bba67b |
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| Record created | 2023-01-20 |
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| Record modified | 2023-03-16 |
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