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Mol Cancer Ther. 2016 Aug;15(8):1879-89. doi: 10.1158/1535-7163.MCT-15-0335. Epub 2016 May 25.

Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells.

Author information

1
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas. Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas. Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Immunology, UT Southwestern Medical Center, Dallas, Texas.
2
Department of Immunology, UT Southwestern Medical Center, Dallas, Texas.
3
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas. Department of Biomedical Engineering, Texas A&M University, College Station, Texas. Department of Immunology, UT Southwestern Medical Center, Dallas, Texas. sally.ward@medicine.tamhsc.edu raimund.ober@tamu.edu.
4
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas. Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas. Department of Immunology, UT Southwestern Medical Center, Dallas, Texas. sally.ward@medicine.tamhsc.edu raimund.ober@tamu.edu.

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 Fcγ receptor (FcγR)-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 FcγR 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. Mol Cancer Ther; 15(8); 1879-89.

PMID:
27226489
PMCID:
PMC4975628
DOI:
10.1158/1535-7163.MCT-15-0335
[Indexed for MEDLINE]
Free PMC Article

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