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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

OBJECTIVE: Natural killer (NK) cells have gained considerable attention due to their potential in treating “cold tumors,” and are therefore considered as one of the new strategies for curing cancer, by using worldwide development of their new possibilities and interventions with NK cell-related ther...

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Autores principales: Cheng, Ying, Zheng, Xiaodong, Wang, Xuefu, Chen, Yongyan, Wei, Haiming, Sun, Rui, Tian, Zhigang, Sun, Haoyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Compuscript 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721099/
https://www.ncbi.nlm.nih.gov/pubmed/33299651
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0399
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author Cheng, Ying
Zheng, Xiaodong
Wang, Xuefu
Chen, Yongyan
Wei, Haiming
Sun, Rui
Tian, Zhigang
Sun, Haoyu
author_facet Cheng, Ying
Zheng, Xiaodong
Wang, Xuefu
Chen, Yongyan
Wei, Haiming
Sun, Rui
Tian, Zhigang
Sun, Haoyu
author_sort Cheng, Ying
collection PubMed
description OBJECTIVE: Natural killer (NK) cells have gained considerable attention due to their potential in treating “cold tumors,” and are therefore considered as one of the new strategies for curing cancer, by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products. METHODS: We constructed a trispecific killer engager (TriKE) consisting of anti-CD16, IL-15, and anti-CD19. This TriKE was designed to attract CD19(+) tumor cells to CD16(+) NK cells, whereas IL-15 sustained the proliferation, development, and survival of NK cells. RESULTS: Treatment with 161519 TriKE in the presence of CD19(+) targets upregulated expression of CD69, CD107a, TRAIL, IFN-γ, and TNF-α in NK cells, and significantly improved the proliferation and cytotoxicity of NK cells. NK cells “armed” with 161519 TriKE showed stronger cytolysis against CD19(+) targets compared with that of “unarmed” NK cells. A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE, when compared with that in control mice or mice treated with 1619 BiKE. Combined use of IL-2 was a more effective treatment with 1619 BiKE, when compared with that using 161519 TriKE. CONCLUSIONS: The newly generated 161519 TriKE enhanced the proliferation, activation, cytokine secretion, and cytotoxicity of NK cells in the presence of CD19(+) tumor cells. The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts, and could be used to treat CD19-positive cancers.
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spelling pubmed-77210992020-12-08 Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers Cheng, Ying Zheng, Xiaodong Wang, Xuefu Chen, Yongyan Wei, Haiming Sun, Rui Tian, Zhigang Sun, Haoyu Cancer Biol Med Original Article OBJECTIVE: Natural killer (NK) cells have gained considerable attention due to their potential in treating “cold tumors,” and are therefore considered as one of the new strategies for curing cancer, by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products. METHODS: We constructed a trispecific killer engager (TriKE) consisting of anti-CD16, IL-15, and anti-CD19. This TriKE was designed to attract CD19(+) tumor cells to CD16(+) NK cells, whereas IL-15 sustained the proliferation, development, and survival of NK cells. RESULTS: Treatment with 161519 TriKE in the presence of CD19(+) targets upregulated expression of CD69, CD107a, TRAIL, IFN-γ, and TNF-α in NK cells, and significantly improved the proliferation and cytotoxicity of NK cells. NK cells “armed” with 161519 TriKE showed stronger cytolysis against CD19(+) targets compared with that of “unarmed” NK cells. A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE, when compared with that in control mice or mice treated with 1619 BiKE. Combined use of IL-2 was a more effective treatment with 1619 BiKE, when compared with that using 161519 TriKE. CONCLUSIONS: The newly generated 161519 TriKE enhanced the proliferation, activation, cytokine secretion, and cytotoxicity of NK cells in the presence of CD19(+) tumor cells. The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts, and could be used to treat CD19-positive cancers. Compuscript 2020-11-15 2020-12-15 /pmc/articles/PMC7721099/ /pubmed/33299651 http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0399 Text en Copyright: © 2020, Cancer Biology & Medicine https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY) 4.0 (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
spellingShingle Original Article
Cheng, Ying
Zheng, Xiaodong
Wang, Xuefu
Chen, Yongyan
Wei, Haiming
Sun, Rui
Tian, Zhigang
Sun, Haoyu
Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title_full Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title_fullStr Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title_full_unstemmed Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title_short Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers
title_sort trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against cd19-positive cancers
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721099/
https://www.ncbi.nlm.nih.gov/pubmed/33299651
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0399
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