ArticlemAbs2017
Functional optimization of agonistic antibodies to OX40 receptor with novel Fc mutations to promote antibody multimerization.
Article in mAbs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Harnessing multivalency and FcγRIIB engagement to augment anti-CD27 immunotherapy.Nature communications · 2025Article
- Enhancement of Protein-Protein Interactions by Destabilizing Mutations Revealed by HDX-MS.Biomolecules · 2025Review
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- Agonistic Bivalent Human scFvs-Fcγ Fusion Antibodies to OX40 Ectodomain Enhance T Cell Activities against Cancer.Vaccines · 2023Article
- Delivering co-stimulatory tumor necrosis factor receptor agonism for cancer immunotherapy: past, current and future perspectives.Frontiers in immunology · 2023Review
- Unlocking the potential of agonist antibodies for treating cancer using antibody engineering.Trends in molecular medicine · 2023Review
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Structural Basis of a Novel Agonistic Anti-OX40 Antibody.Biomolecules · 2022Article
- Antibody-Targeted TNFRSF Activation for Cancer Immunotherapy: The Role of FcγRIIB Cross-Linking.Frontiers in pharmacology · 2022Review
- Agonist antibody discovery: Experimental, computational, and rational engineering approaches.Drug discovery today · 2022Review
- Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Development of Therapeutic Antibodies and Modulating the Characteristics of Therapeutic Antibodies to Maximize the Therapeutic Efficacy.Biotechnology and bioprocess engineering : BBE · 2021Review
- Development and characterization of a novel anti-OX40 antibody for potent immune activation.Cancer immunology, immunotherapy : CII · 2020Article
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Recent updates on cancer immunotherapy.Precision clinical medicine · 2018Review
- The promise and challenges of immune agonist antibody development in cancer.Nature reviews. Drug discovery · 2018Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising targets for cancer immunotherapies. To optimize the agonism of therapeutic antibodies to these receptors, Fc engineering of antibodies was applied to facilitate the clustering of cell surface TNFRs to activate downstream signaling pathways. One engineering strategy is to identify Fc mutations that facilitate antibody multimerization on the cell surface directly. From the analyses of the crystal packing of IgG1 structures, we identified a novel set of Fc mutations, T437R and K248E, that facilitated antibody multimerization upon binding to antigens on cell surface. In a NF-κB reporter assay, the engineered T437R/K248E mutations could facilitate enhanced agonism of an anti-OX40 antibody without the dependence on FcγRIIB crosslinking. Nonetheless, the presence of cells expressing FcγRIIB could facilitate a boost of the agonism of the engineered antibody with mutations on IgG1 Fc, but not on the silent IgG2σ Fc. The Fc engineered antibody also showed enhanced effector functions, including antibody-dependent cell-meditated cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity, depending on the IgG subtypes. Also, the engineered antibodies showed normal FcRn binding and pharmacokinetic profiles in mice. In summary, this study elucidated a novel Fc engineering approach to promote antibody multimerization on a cell surface, which could enhance agonism and improve effector function for anti-TNFR antibodies as well as other therapeutic antibodies.
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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.