Macrophage-mediated trogocytosis leads to death of antibody-opsonized tumor cells
Macrophage-mediated trogocytosis leads to death of antibody-opsonized tumor cells
Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcg receptor (FcgR)-mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells. Further, antibody engineering to increase FcgR interactions enhances this tumoricidal activity. These studies extend the complex repertoire of activities of macrophages to trogocytic-mediated cell death of HER2-overexpressing target cells and have implications for the development of effective antibody-based therapies.
1879-1889
Velmurugan, Ramraj
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Challa, Dilip K.
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Ram, Sripad
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Ober, Raimund J.
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Ward, E. Sally
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1 August 2016
Velmurugan, Ramraj
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Challa, Dilip K.
433af413-17a0-4c55-b86f-21e4e5cedd6f
Ram, Sripad
559bd560-3817-4e53-8c7a-2f08e4518412
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
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Velmurugan, Ramraj, Challa, Dilip K., Ram, Sripad, Ober, Raimund J. and Ward, E. Sally
(2016)
Macrophage-mediated trogocytosis leads to death of antibody-opsonized tumor cells.
Molecular Cancer Therapeutics, 15 (8), .
(doi:10.1158/1535-7163.MCT-15-0335).
Abstract
Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcg receptor (FcgR)-mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells. Further, antibody engineering to increase FcgR interactions enhances this tumoricidal activity. These studies extend the complex repertoire of activities of macrophages to trogocytic-mediated cell death of HER2-overexpressing target cells and have implications for the development of effective antibody-based therapies.
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More information
Accepted/In Press date: 17 May 2016
e-pub ahead of print date: 25 May 2016
Published date: 1 August 2016
Identifiers
Local EPrints ID: 423672
URI: http://eprints.soton.ac.uk/id/eprint/423672
ISSN: 1535-7163
PURE UUID: a5ed7f19-e0bc-4363-bdec-03ab659b4342
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Date deposited: 27 Sep 2018 16:30
Last modified: 18 Mar 2024 03:48
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Contributors
Author:
Ramraj Velmurugan
Author:
Dilip K. Challa
Author:
Sripad Ram
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