ArticleScientific reports2022
Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Article
- T cell engagers control solid tumors through clonal replacement and IL2-driven effector differentiation of CD8 T cells.bioRxiv : the preprint server for biology · 2026Article
- In vivo genome-wide CRISPR screens in human T cells to enhance T cell therapy for solid tumors.bioRxiv : the preprint server for biology · 2025Article
- Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A novel label-free method to determine equilibrium dissociation constants of antibodies binding to cell surface proteins.Scientific reports · 2025Article
- Article
- Rapid Generation of Murine Bispecific Antibodies Using FAST-IgAntibodies (Basel, Switzerland) · 2024Article
- T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors.Nature communications · 2024Article
- Structural and functional characterization of IgG- and non-IgG-based T-cell-engaging bispecific antibodies.Frontiers in immunology · 2024Article
- CD3ε of a pan T cell marker involved in mouseInternational journal of ophthalmology · 2024Article
- Bispecific Antibodies Produced via Chemical Site-Specific Conjugation Technology: AJICAP Second-Generation.ACS medicinal chemistry letters · 2023Article
- Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models.Journal for immunotherapy of cancer · 2023Article
- Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy.mAbsArticle
- Article
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Authors and funding
26 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell engagers (TCEs) are a growing class of biotherapeutics being investigated in the clinic for treatment of a variety of hematological and solid tumor indications. However, preclinical evaluation of TCEs in vivo has been mostly limited to xenograft tumor models in human T-cell reconstituted immunodeficient mice, which have a number of limitations. To explore the efficacy of human TCEs in fully immunocompetent hosts, we developed a knock-in mouse model (hCD3E-epi) in which a 5-residue N-terminal fragment of murine CD3-epsilon was replaced with an 11-residue stretch from the human sequence that encodes for a common epitope recognized by anti-human CD3E antibodies in the clinic. T cells from hCD3E-epi mice underwent normal thymic development and could be efficiently activated upon crosslinking of the T-cell receptor with anti-human CD3E antibodies in vitro. Furthermore, a TCE targeting human CD3E and murine CD20 induced robust T-cell redirected killing of murine CD20-positive B cells in ex vivo hCD3E-epi splenocyte cultures, and also depleted nearly 100% of peripheral B cells for up to 7 days following in vivo administration. These results highlight the utility of this novel mouse model for exploring the efficacy of human TCEs in vivo, and suggest a useful tool for evaluating TCEs in combination with immuno-oncology/non-immuno-oncology agents against heme and solid tumor targets in hosts with a fully intact immune system.
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