Abstract
CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages.
MeSH terms
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Animals
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Antibodies, Monoclonal, Humanized / immunology*
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Cell Line, Tumor
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Cytokines / genetics
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Cytokines / metabolism
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Humans
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Hyaluronan Receptors / immunology*
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Macrophages / immunology*
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Mice
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Mice, SCID
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / immunology
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Phagocytosis
Substances
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Antibodies, Monoclonal, Humanized
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Cytokines
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Hyaluronan Receptors
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RG7356
Grants and funding
Roche Innovation Center Munich provided support in the form of salaries for authors DM, FB, EV, AN, SB, TF, BG, SW, and VR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the "Author Contributions" section. Selventa Inc. provided support in the form of salary for author DL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the "Author Contributions" section.