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Open AccessArticle

An Fc-Optimized CD133 Antibody for Induction of Natural Killer Cell Reactivity Against Colorectal Cancer

1
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner site, 72076 Tuebingen, Germany
2
DFG Cluster of Excellence 2180 “Image-guided and Functional Instructed Tumor Therapy (iFIT)”, 72076 Tuebingen, Germany
3
Department for Immunology, Eberhard Karls University, 72076 Tuebingen, Germany
4
Department of Hematology and Oncology, Eberhard Karls University, 72076 Tuebingen, Germany
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
Cancers 2019, 11(6), 789; https://doi.org/10.3390/cancers11060789
Received: 13 May 2019 / Revised: 28 May 2019 / Accepted: 5 June 2019 / Published: 7 June 2019
The introduction of monoclonal antibodies (mAbs) has largely improved treatment options for cancer patients. The ability of antitumor mAbs to elicit antibody-dependent cellular cytotoxicity (ADCC) contributes to a large extent to their therapeutic efficacy. Many efforts accordingly aim to improve this important function by engineering mAbs with Fc parts that display enhanced affinity to the Fc receptor CD16 expressed, e.g., on natural killer (NK) cells. Here we characterized the CD133 mAb 293C3-SDIE that contains an engineered Fc part modified by the amino acid exchanges S239D/I332E—that reportedly increase the affinity to CD16—with regard to its ability to induce NK reactivity against colorectal cancer (CRC). 293C3-SDIE was found to be a stable protein with favorable binding characteristics achieving saturating binding to CRC cells at concentrations of approximately 1 µg/mL. While not directly affecting CRC cell growth and viability, 293C3-SDIE potently induced NK cell activation, degranulation, secretion of Interferon-γ, as well as ADCC resulting in potent lysis of CRC cell lines. Based on the preclinical characterization presented in this study and the available data indicating that CD133 is broadly expressed in CRC and represents a negative prognostic marker, we conclude that 293C3-SDIE constitutes a promising therapeutic agent for the treatment of CRC and thus warrants clinical evaluation. View Full-Text
Keywords: colorectal cancer; immunotherapy; antibody; NK cells; ADCC; CD133; prominin-1 colorectal cancer; immunotherapy; antibody; NK cells; ADCC; CD133; prominin-1
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Schmied, B.J.; Riegg, F.; Zekri, L.; Grosse-Hovest, L.; Bühring, H.-J.; Jung, G.; Salih, H.R. An Fc-Optimized CD133 Antibody for Induction of Natural Killer Cell Reactivity Against Colorectal Cancer. Cancers 2019, 11, 789.

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