ArticlemAbs
A novel conditional active biologic anti-EpCAM x anti-CD3 bispecific antibody with synergistic tumor selectivity for cancer immunotherapy.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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
23 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.Cell communication and signaling : CCS · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours.British journal of cancer · 2026Review
- Immunotherapy resistance in colorectal cancer: therapeutic strategies and biomarker-guided approaches.Cancer cell international · 2026Review
- Efficacy and safety of approved cellular therapies and bispecific antibodies in solid tumors: the current state.Discover oncology · 2026Review
- T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.Frontiers in immunology · 2026Review
- Emerging precision medicine in multiple myeloma: clinical and preclinical landscape of T cell, natural killer cell, and macrophages engaging multi-specific antibodies.Frontiers in immunology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- A comprehensive analysis of humanized mouse models for the study of cancer immunotherapies.Frontiers in immunology · 2026Article
- The acidic tumor microenvironment in hepatocellular carcinoma: a barrier to adoptive cellular immunotherapy.Frontiers in immunology · 2026Review
- Revolutionizing cancer immunotherapy: T cell engagers beyond hematologic malignancies toward solid tumors.Frontiers in immunology · 2026Review
- Article
- Review
- Article
- T cell engagers: expanding horizons in oncology and beyond.British journal of cancer · 2025Review
- Bispecific Antibodies in Solid Tumors: Advances and Challenges.International journal of molecular sciences · 2025Review
- Preclinical development of mecbotamab vedotin (BA3011), a novel, AXL-specific conditional active biologic antibody-drug conjugate.Antibody therapeutics · 2025Article
- Immune analysis according to Lauren type for gastric cancer and its significance in individual treatment and prognostic prediction.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that plays several roles in cancer biology. EpCAM is an attractive therapeutic target because of its expression in most solid tumors. However, targeting EpCAM has been challenging because it is also highly expressed in normal epithelial tissues. Initial attempts to develop EpCAM-specific T-cell engagers were unsuccessful due to severe cytokine release effects, as well as serious on-target, off-tumor drug-related toxicities. We developed novel, conditionally active biological (CAB) bispecific antibodies that bind to both EpCAM and CD3 in an acidic tumor microenvironment. In healthy tissues, binding to EpCAM and CD3 is greatly reduced by a novel, dual CAB selection, where each binding domain is independently blocked by the presence of physiological chemicals known as Protein-associated Chemical Switches (PaCS). The CAB anti-EpCAM T-cell engagers displayed the anticipated bispecific binding properties and mediated the potent lysis of EpCAM-positive cancer cell lines through the recruitment of T cells in the tumor microenvironment. Xenograft studies showed that the efficacy of CAB bispecific antibodies is similar to that of a non-CAB anti-EpCAM bispecific antibody, but they have markedly reduced toxicity in non-human primates, indicating an unprecedentedly widened therapeutic index of over 100-fold. These preclinical results indicate that the dual CAB bispecific antibody is potentially both a powerful and safe therapeutic platform and a promising T cell-engaging treatment for patients with EpCAM-expressing tumors.
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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.