catumaxomab

Catumaxomab is a trifunctional monoclonal antibody used to treat malignant ascites in adults with EpCAM-positive carcinomas. It is a chimeric antibody combining two antigen specificities and an intact Fc region: one binding EpCAM on tumor cells, one engaging CD3 on T cells, and an Fc portion that interacts with Fc gamma receptors on accessory cells such as macrophages and dendritic cells. This design brings tumor cells, T cells, and accessory cells into a single immunological synapse, promoting tumor cell killing and immune activation.

Mechanism and structure: By simultaneously binding EpCAM, CD3, and Fc receptors, catumaxomab recruits a polyclonal immune response and local antigen presentation within the peritoneal cavity. The intraperitoneal engagement aims to reduce malignant ascites and foster an anti-tumor immune environment, with the goal of controlling disease progression while relieving fluid buildup.

Indication and administration: Catumaxomab is administered intraperitoneally via catheter, with a stepwise escalating dosing schedule over several days after abdominocentesis to drain ascites. Dosing is individualized, and patients are closely monitored for toxicity, particularly cytokine release symptoms. Premedication and supportive care are commonly used, and treatment may be discontinued for severe adverse events or lack of response.

Safety and contraindications: Common adverse events include fever, abdominal pain, nausea, vomiting, fatigue, and hypotension, along with cytokine-related symptoms. Serious infections or peritoneal inflammation can occur. The therapy is contraindicated in patients with uncontrolled infections, extensive peritoneal metastasis causing obstruction, or EpCAM-negative ascites.

History and status: Catumaxomab (brand Removab) was developed for EU approval as a treatment for malignant ascites due to EpCAM-positive cancers. Availability and regulatory status vary by country, and use has been limited by safety considerations and practical administration requirements.