Trifunctional antibody
A type of monoclonal antibody used in cancer treatment
Trifunctional antibodies are a class of monoclonal antibodies designed to engage three different types of cells to enhance the immune response against cancer cells. These antibodies are engineered to bind to two different antigens and recruit immune effector cells, thereby facilitating the destruction of tumor cells.
Mechanism of action
Trifunctional antibodies are unique in their ability to simultaneously bind to three different targets. Typically, one arm of the antibody binds to a tumor-associated antigen on the cancer cell, while the other arm binds to an antigen on an immune cell, such as a T cell or a natural killer cell. The Fc region of the antibody can also bind to Fc receptors on macrophages and other immune cells. This tri-specific binding facilitates the formation of a cytotoxic synapse between the immune cells and the cancer cells, leading to the targeted destruction of the tumor cells.
Development and applications
Trifunctional antibodies are developed using quadroma technology, which involves the fusion of two different hybridoma cells, each producing a different monoclonal antibody. This results in a single antibody with two different antigen-binding sites. The first trifunctional antibody to be approved for clinical use was catumaxomab, which targets the EpCAM antigen on tumor cells and the CD3 antigen on T cells.
Clinical use
Catumaxomab has been used in the treatment of malignant ascites in patients with EpCAM-positive tumors. The antibody facilitates the recruitment of T cells and other immune effector cells to the site of the tumor, enhancing the immune-mediated destruction of cancer cells. Clinical trials have demonstrated the efficacy of catumaxomab in reducing ascites and improving patient outcomes.
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Contributors: Prab R. Tumpati, MD