ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Selection of High-Affinity Heterodimeric Antigen-Binding Fc Fragments from a Large Yeast Display Library.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Bispecific mAbInternational journal of molecular sciences · 2022Article
- Bispecific antibodies with Fab-arms featuring exchanged antigen-binding constant domains.Biochemistry and biophysics reports · 2021Article
- Molecular Mechanism of HER2 Rapid Internalization and Redirected Trafficking Induced by Anti-HER2 Biparatopic Antibody.Antibodies (Basel, Switzerland) · 2020Article
- Identification of an Activating Mutation in the Extracellular Domain of HER2 Conferring Resistance to Pertuzumab.OncoTargets and therapy · 2019Article
- Article
- Current progress in innovative engineered antibodies.Protein & cell · 2018Review
- Article
- Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds.Frontiers in immunology · 2017Review
- Engineered Soluble Monomeric IgG1 Fc with Significantly Decreased Non-Specific Binding.Frontiers in immunology · 2017Article
- Engineered IgG1-Fc--one fragment to bind them all.Immunological reviews · 2016Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 with high affinity and recognizes an epitope that does not overlap with those of trastuzumab or pertuzumab. In tumor cells that express high levels of HER2, FS102 caused profound HER2 internalization and degradation leading to tumor cell apoptosis. The antitumor effect of FS102 in patient-derived xenografts (PDXs) correlated strongly with the HER2 amplification status of the tumors. Superior activity of FS102 over trastuzumab or the combination of trastuzumab and pertuzumab was observed in vitro and in vivo when the gene copy number of HER2 was equal to or exceeded 10 per cell based on quantitative polymerase chain reaction (qPCR). Thus, FS102 induced complete and sustained tumor regression in a significant proportion of HER2-high PDX tumor models. We hypothesize that the unique structure and/or epitope of FS102 enables the Fcab to internalize and degrade cell surface HER2 more efficiently than standard of care antibodies. In turn, increased depletion of HER2 commits the cells to apoptosis as a result of oncogene shock. FS102 has the potential of a biomarker-driven therapeutic that derives superior antitumor effects from a unique mechanism-of-action in tumor cells which are oncogenically addicted to the HER2 pathway due to overexpression.
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Registered trials
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.