ArticleCancer immunology, immunotherapy : CII2021
Mechanism of action of a T cell-dependent bispecific antibody as a breakthrough immunotherapy against refractory colorectal cancer with an oncogenic mutation.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Measurement of T Cell Migration by T Cell-Dependent Bispecific Antibody in Cancer Cells and T Cell Cross-Linking.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Fluorescent-Based Analysis of T Cells and T-Cell-Dependent Bispecific Antibody in a Brain Tumor Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Advanced Evaluation of T-Cell-Dependent Bispecific Antibodies Using Fluorescence Imaging and In Vivo Models.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Optimized In Vitro T-Cell Exhaustion Assay for Evaluating T-Cell-Dependent Bispecific Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Visualization of Immunological Synapse Formation by Intercellular Cross-Linking of T Cell-Dependent Bispecific Antibodies Using Fluorescence Microscopy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Regulatory dynamics of Th17 lymphocytes in oral squamous cell carcinoma: immune modulation and emerging immunotherapies.Immunologic research · 2025Review
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- CD3-engaging bispecific antibodies trigger a paracrine regulated wave of T-cell recruitment for effective tumor killing.Communications biology · 2024Article
- Bispecific Antibodies Produced via Chemical Site-Specific Conjugation Technology: AJICAP Second-Generation.ACS medicinal chemistry letters · 2023Article
- Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.Acta pharmaceutica Sinica. B · 2023Review
- Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response.Scientific reports · 2023Article
- Tumor-targeted superantigens produce curative tumor immunity with induction of memory and demonstrated antigen spreading.Journal of translational medicine · 2023Article
- Redirecting Polyclonal T Cells against Cancer with Soluble T-Cell Receptors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Recent advances in immunotherapy and molecular targeted therapy for gastric cancer.Future science OA · 2023Review
- A Probody T Cell-Engaging Bispecific Antibody Targeting EGFR and CD3 Inhibits Colon Cancer Growth with Limited Toxicity.Cancer research · 2022Article
- T Cell Bispecific Antibodies: An Antibody-Based Delivery System for Inducing Antitumor Immunity.Pharmaceuticals (Basel, Switzerland) · 2021Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
T cell-dependent bispecific antibody (TDB)-induced T cell activation, which can eliminate tumor cells independent of MHC engagement, is expected to be a novel breakthrough immunotherapy against refractory cancer. However, the mechanism of action of TDBs has not been fully elucidated thus far. We focused on TDB-induced T cell-tumor cell contact as an important initial step in direct T cell-mediated tumor cell killing via transport of cytotoxic cell proteases (e.g., granzymes) with or without immunological synapse formation. Using an anti-EGFR/CD3 TDB, hEx3, we visualized and quantified T cell-tumor cell contact and demonstrated a correlation between the degree of cell contact and TDB efficacy. We also found that cytokines, including interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) secreted by activated T cells, damaged tumor cells in a cell contact-independent manner. Moreover, therapeutic experiences clearly indicated that hEx3, unlike conventional anti-EGFR antibodies, was effective against colorectal cancer (CRC) cells with mutant KRAS, BRAF, or PIK3CA. In a pharmacokinetic analysis, T cells spread gradually in accordance with the hEx3 distribution within tumor tissue. Accordingly, we propose that TDBs should have four action steps: 1st, passive targeting via size-dependent tumor accumulation; 2nd, active targeting via specific binding to tumor cells; 3rd, T cell redirection toward tumor cells; and 4th, TDB-induced cell contact-dependent (direct) or -independent (indirect) tumor cell killing. Finally, our TDB hEx3 may be a promising reagent against refractory CRC with an oncogenic mutation associated with a poor prognosis.
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