ArticleOncotarget2016
Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fcγ receptors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 76 citations in OpenAlex.
- Article
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- Preclinical Evaluation of AHT-102, a CLDN18.2 × CD3 Bispecific Antibody: Pharmacokinetics, Anti-Tumor Efficacy, Tissue Distribution, and Safety Profile.Drugs in R&D · 2026Article
- Recent advances in bispecific antibody-drug conjugates for breast cancer therapy.Cancer chemotherapy and pharmacology · 2026Review
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- Clinical Development of T-Cell Bispecific Antibodies: Review, Challenges, and Prospective Solutions in Solid Tumor.Methods in molecular biology (Clifton, N.J.) · 2026Review
- High-risk neuroblastoma as a model for immunotherapy of non-immunogenic cancers: where might we be in 20 years?Journal for immunotherapy of cancer · 2025Review
- Recent advances in therapeutic cancer vaccines.Nature reviews. Cancer · 2025Review
- Cancer vaccines compensate for the insufficient induction of protective tumor-specific immunity of CD3 bispecific antibody therapy.Journal for immunotherapy of cancer · 2025Article
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- Current landscape of T-cell engagers in early-phase clinical development in solid cancers.Frontiers in immunology · 2025Review
- Advances in adoptive cell therapies in small cell lung cancer.Exploration of targeted anti-tumor therapy · 2025Review
- Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.Molecular diagnosis & therapy · 2024Review
- Bispecific antibodies for multiple myeloma: past, present and future.International journal of hematology · 2024Review
- Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data.Science advances · 2024Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Impact of tissue penetration and albumin binding on design of T cell targeted bispecific agents.Neoplasia (New York, N.Y.) · 2024Article
- Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment.Cancers · 2024Review
- Advances in the treatment of malignant ascites in China.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunotherapeutic catumaxomab targets EpCAM positive cancers and is approved for the treatment of peritoneal carcinomatosis. To assess the safety of intravenous applications a phase 1 clinical trial was initiated. Treatment of EpCAM positive tumor patients with catumaxomab caused dose dependent hepatitis as evidenced by significant elevations in serum alanine- and aspartate aminotransferases, bilirubin, γGT and induction of the acute phase C-reactive protein (CRP) and the cytokines IL6 and IL8. The first patient receiving 10μg catumaxomab experienced fatal acute liver failure which led to the termination of the study. Immmunopathology revealed catumaxomab to bind via its Fc-fragment to FcγR-positive Kupffer cells to stimulate CRP, chemokine and cytokine release. The observed CD3+T-cell margination at activated hepatic macrophages exacerbated T-cell mediated cytotoxicity. Strikingly, the combined Kupffer/T-cell responses against liver cells did not require hepatocytes to be EpCAM-positive. Catumaxomab's off-target activity involved T-cell mediated lysis of the granzyme B cell death pathway and the molecular interaction of hepatic sinusoidal macrophages with T-cells induced cytolytic hepatitis. Although the bile ducts were surrounded by densely packed lymphocytes these rarely infiltrated the ducts to suggest an intrahepatic cholestasis as the cause of hyperbilirubinaemia. Lastly, evidence for the programming of memory T-cells was observed with one patient that succumbed to his cancer six weeks after the last catumaxomab infusion. In conclusion, our study exemplifies off-target hepatotoxicity with molecularly targeted therapy and highlights the complexities in the clinical development of immunotherapeutic antibodies.
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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.