ArticleCancer science2010
Fc-engineered EGF-R antibodies mediate improved antibody-dependent cellular cytotoxicity (ADCC) against KRAS-mutated tumor cells.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Trial
- Multifactorial pharmacogenetic analysis in colorectal cancer patients receiving 5-fluorouracil-based therapy together with cetuximab-irinotecan.British journal of clinical pharmacology · 2012Trial
- Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells.Journal of oncology · 2022Article
- Enhancement of epidermal growth factor receptor antibody tumor immunotherapy by glutaminyl cyclase inhibition to interfere with CD47/signal regulatory protein alpha interactions.Cancer science · 2021Article
- Article
- CD8Current opinion in chemical engineering · 2018Article
- A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses.Clinical & translational immunology · 2016Article
- A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism.The Journal of biological chemistry · 2015Article
- Targeting the K-Ras--JNK axis eliminates cancer stem-like cells and prevents pancreatic tumor formation.Oncotarget · 2014Article
- Computational design of a CNT carrier for a high affinity bispecific anti-HER2 antibody based on trastuzumab and pertuzumab Fabs.Journal of molecular modeling · 2013Article
- Identification of dominant antibody-dependent cell-mediated cytotoxicity epitopes on the hemagglutinin antigen of pandemic H1N1 influenza virus.Journal of virology · 2013Article
- scFv-based "Grababody" as a general strategy to improve recruitment of immune effector cells to antibody-targeted tumors.Cancer research · 2013Article
- Oncogenic KRAS impairs EGFR antibodies' efficiency by C/EBPβ-dependent suppression of EGFR expression.Neoplasia (New York, N.Y.) · 2012Article
- The use of epidermal growth factor receptor monoclonal antibodies in squamous cell carcinoma of the head and neck.Chemotherapy research and practice · 2012Article
- Progress in metastatic colorectal cancer: growing role of cetuximab to optimize clinical outcome.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2010Review
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic mutations of the KRAS gene have emerged as a common mechanism of resistance against epidermal growth factor receptor (EGF-R)-directed tumor therapy. Mutated KRAS leads to ligand-independent activation of signaling pathways downstream of EGF-R. Thereby, direct effector mechanisms of EGF-R antibodies, such as blockade of ligand binding and inhibition of signaling, are bypassed. Thus, a humanized variant of the approved EGF-R antibody Cetuximab inhibited growth of wild-type KRAS-expressing A431 cells, but did not inhibit KRAS-mutated A549 tumor cells. We then investigated whether killing of tumor cells harboring mutated KRAS can be improved by enhancing antibody-dependent cellular cytotoxicity (ADCC). Protein- and glyco-engineering of antibodies' Fc region are established technologies to enhance ADCC by increasing antibodies' affinity to activating Fcgamma receptors. Thus, EGF-R antibody variants with increased affinity for the natural killer (NK) cell-expressed FcgammaRIIIa (CD16) were generated and analyzed. These variants triggered significantly enhanced mononuclear cell (MNC)-mediated killing of KRAS-mutated tumor cells compared to wild-type antibodies. Additionally, cells transfected with mutated KRAS were killed as effectively by ADCC as vector-transfected control cells. Together, these data demonstrate that KRAS mutations are not sufficient to render tumor cells resistant to ADCC. Consequently Fc-engineered EGF-R antibodies may prove effective against KRAS-mutated tumors, which are not susceptible to signaling inhibition by EGF-R antibodies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.