ArticlemAbs
Structure-based engineering of a novel CD3ε-targeting antibody for reduced polyreactivity.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Emission from CT State and J-aggregates in a Model Coumarin-Paraben Conjugate: A Spectroscopic Study.Journal of fluorescence · 2026Article
- Immunomodulatory functions of glutaminyl cyclases QPCTL and QPCT.Frontiers in immunology · 2026Review
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Article
- Review
- Development and clinical trial of M701, an Anti-EpCAM × Anti-CD3 bispecific antibody: a targeted intraperitoneal therapy for malignant ascites stemming from advanced solid tumors.Experimental hematology & oncology · 2025Article
- Antibody-Antigen Epitope Mapping by X-Ray Crystallography.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Rapid Generation of Murine Bispecific Antibodies Using FAST-IgAntibodies (Basel, Switzerland) · 2024Article
- IMGT/mAb-KG: the knowledge graph for therapeutic monoclonal antibodies.Frontiers in immunology · 2024Article
- Profiling the Biophysical Developability Properties of Common IgG1 Fc Effector Silencing Variants.Antibodies (Basel, Switzerland) · 2023Article
- Review
- Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy.mAbsArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bispecific antibodies continue to represent a growth area for antibody therapeutics, with roughly a third of molecules in clinical development being T-cell engagers that use an anti-CD3 binding arm. CD3 antibodies possessing cross-reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N-terminus of CD3 epsilon (CD3ε). Such antibodies have high isoelectric points and display problematic polyreactivity (correlated with poor pharmacokinetics for monospecific antibodies). Using insights from the crystal structure of anti-Hu/Cy CD3 antibody ADI-26906 in complex with CD3ε and antibody engineering using a yeast-based platform, we have derived high-affinity CD3 antibody variants with very low polyreactivity and significantly improved biophysical developability. Comparison of these variants with CD3 antibodies in the clinic (as part of bi- or multi-specifics) shows that affinity for CD3 is correlated with polyreactivity. Our engineered CD3 antibodies break this correlation, forming a broad affinity range with no to low polyreactivity. Such antibodies will enable bispecifics with improved pharmacokinetic and safety profiles and suggest engineering solutions that will benefit the large and growing sector of T-cell engagers.
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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.