Catumaxomab for Malignant Ascites Associated With Gastric Cancer
Trifunctional antibodies such as catumaxomab may have a significant impact in treating these malignancies.
Monoclonal antibodies (mAbs) are a growing class of medications used to treat a multitude of disease states, ranging from autoimmune diseases to cancer. There are over 40 mAbs marketed, with almost $100 billion worth of sales in the world.1 Although mAbs are a technical and clinical breakthrough, their utility is limited by the inability to target more than 1 cell mediator or pathway at the same time. This can lead to inefficient killing of cancer cells and the development of resistance.
In attempts to improve these inefficiencies, a new subtype of mAbs—trifunctional antibodies—are increasingly being studied in the development pipeline of several pharmaceutical companies. Catumaxomab is 1 of the earliest trifunctional antibodies developed for use in patients with malignant ascites.2
The binding arms of catumaxomab are unique in that each of the 2 arms binds 2 different targets. Traditionally, each arm (fragment antigen binding [Fab]) would bind the same target while the fragment crystallizable (Fc) region would interact with the cell surface receptor and/or the complement system.
With catumaxomab, 1 of the Fab arms binds epithelial cell adhesion molecule (EpCAM), which is a glycoprotein expressed on the surface of some types of cancer cells.3 The second Fab arm binds to cluster of differentiation 3 (CD3) on T cells, which helps activate the body's immune response against cancer. The Fc portion of the antibody binds to macrophages or natural killer cells, which help coordinate the attack on the tumor cells. The structure of catumaxomab is therefore a unique opportunity, bringing 3 different cell types together to make anticancer treatment more efficient and efficacious.
Malignancy is the underlying cause of ascites in up to 10% of all patients.4 The cancers most commonly associated with malignant ascites include ovarian, breast, gastric, and colorectal.5 Malignancy-related ascites is typically difficult to manage, with limited treatment options including diuretics and repeated large volume paracenteses, which can have a significant impact on a patient's quality of life.