ArticleJournal of experimental & clinical cancer research : CR2022
Novel tri-specific tribodies induce strong T cell activation and anti-tumor effects in vitro and in vivo.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
- Proteogenomic analysis of the CALGB 40601 (Alliance) HER2+ breast cancer neoadjuvant trial reveals resistance biomarkers.Cell reports. Medicine · 2025Trial
- Immunotherapy in cervical cancer: From the view of scientometric analysis and clinical trials.Frontiers in immunology · 2023Trial
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- Human germline-like monoclonal antibody against 5T4 enables potent ADC and CAR-T therapies for solid tumors.Acta pharmacologica Sinica · 2026Article
- Evidence of Cardiotoxic Immune Activation by Triple Immune Checkpoint Blockade: A Translational Alert for Clinical Surveillance in Patients With Cancer.Journal of cardiovascular pharmacology · 2026Article
- Revolutionizing cancer immunotherapy: T cell engagers beyond hematologic malignancies toward solid tumors.Frontiers in immunology · 2026Review
- Bispecific Radioligands (BRLs): Two Is Better Than One.Journal of clinical medicine · 2025Review
- Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Bispecific antibody targeting CD155 mediates T-cell immunotherapy against human gynecological malignancies.Investigational new drugs · 2025Article
- Tri-specific tribodies targeting 5T4, CD3, and immune checkpoint drive stronger functional T-cell responses than combinations of antibody therapeutics.Cell death discovery · 2025Article
- Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Facile Access to Branched Multispecific Proteins.Bioconjugate chemistry · 2024Article
- Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Comparative Analysis of a Human Neutralizing mAb Specific for SARS-CoV-2 Spike-RBD with Cilgavimab and Tixagevimab for the Efficacy on the Omicron Variant in Neutralizing and Detection Assays.International journal of molecular sciences · 2023Article
- Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment.Frontiers in immunology · 2023Review
- Better, Faster, Stronger: Accelerating mRNA-Based Immunotherapies With Nanocarriers.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunotherapy based on Bi-specific T Cell Engagers (TCE) represents one of the most attractive strategy to treat cancers resistant to conventional therapies. TCE are antibody-like proteins that simultaneously bind with one arm to a Tumor Associated Antigen (TAA) on cancer cells and with the other one to CD3 complex on a T-cell to form a TCR-independent immune synapse and circumvent Human Leucocyte Antigen restriction. Among them, the tribodies, such as Tb535H, a bi-specific molecule, made up of a Fab and a scFv domain both targeting 5T4 and another scFv targeting CD3, have demonstrated anti-tumor efficacy in preclinical studies.
methodsHere, we generated five novel tri-specific and multi-functional tribodies, called 53X tribodies, composed of a 5T4 binding Fab arm and a CD3 binding scFv, but differently from the parental Tb535H, they contain an additional scFv derived from an antibody specific for an immune checkpoint, such as PD-1, PD-L1 or LAG-3.
resultsCompared with the parental Tb535H bi-specific T cell engager targeting 5T4, the novel 53X tribodies retained similar binding properties of Tb535H tribody, but showed enhanced anti-tumor potency due to the incorporation of the checkpoint inhibitory moiety. In particular, one of them, called 53L10, a tri-specific T cell engager targeting 5T4, CD3 and PD-L1, showed the most promising anti-tumor efficacy in vitro and led to complete tumor regression in vivo.
conclusionsThe novel tribodies have the potential to become strong and safe therapeutic drugs, allowing to reduce also the cost of production as one single molecule contains three different specificities including the anti-TAA, anti-CD3 and anti-IC binding arms.
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