ArticleThe Journal of biological chemistry2016
Fc Engineering Approaches to Enhance the Agonism and Effector Functions of an Anti-OX40 Antibody.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- 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
- Review
- Dual targeting OX40 and IL-2 receptor enhances antitumor activity through tumor-infiltrating Treg depletion and CD8Journal for immunotherapy of cancer · 2025Article
- Identification of anti-mouse PD-1 agonist antibodies that inhibit T cell activation.Frontiers in immunology · 2025Article
- OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress.Frontiers in oncology · 2025Review
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Characterization of a novel anti-PVRIG antibody with Fc-competent function that exerts strong antitumor effects via NK activation in preclinical models.Cancer immunology, immunotherapy : CII · 2024Article
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- Antibody-Drug Conjugates in Gynecologic Cancers.Current treatment options in oncology · 2024Review
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
- Fc-Engineered Therapeutic Antibodies: Recent Advances and Future Directions.Pharmaceutics · 2023Review
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- 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
- Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells.Communications biology · 2022Article
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Logic-gated antibody pairs that selectively act on cells co-expressing two antigens.Nature biotechnology · 2022Article
- Finding the Right Heavy Chains for Immunostimulatory Antibodies.International journal of molecular sciences · 2022Review
- Antibody homotypic interactions are encoded by germline light chain complementarity determining region 2.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Agonistic antibodies directed against immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising cancer immunotherapies. Several Fc engineering approaches discovered recently can augment the anti-tumor activities of TNFR antibodies by enhancing their agonistic activities and/or effector functions. In this study, we compared these approaches for their effects on an anti-OX40 antibody. Both S267E/L328F and V12 mutations facilitated enhanced binding to FcγRIIB and thus increased FcγRIIB cross-linking mediated agonist activity. However, both mutations abrogated the binding to FcγRIIIA and thereby decreasing the antibody-dependent cellular cytotoxicity activities. In contrast, the E345R mutation, which can promote antibody multimerization upon receptor binding, facilitated anti-OX40 antibody to have increased agonism by promoting the clustering of OX40 receptors without the dependence on FcγRIIB cross-linking. Nonetheless, cross-linking to FcγRIIB can lead to a further boost of the agonism of the anti-OX40 antibody with IgG1 Fc but not with the silent IgG2σ Fc. The antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activities of the anti-OX40 antibody with the E345R mutation were affected by the choice of IgG subtypes. However, there was little change in the antibody-dependent cellular phagocytosis activity. In summary, different Fc engineering approaches can guide the design of engineered antibodies to OX40 and other TNFR with improved anti-tumor activity.
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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.