What Is Rituximab, and What Is Its Mechanism of Action?

Cancer cells contain various molecules that distinguish them from normal cells. These are mainly protein receptors on cell surfaces. Monoclonal antibodies developed against these proteins have become among the most effective cancer medicines in recent years.

Antibodies are proteins produced by the immune system to protect us from pathogens and cancer cells. Since the 1970s, these highly selective purified molecules have also been produced in laboratories and are called monoclonal antibodies .

Approximately 20 monoclonal antibodies have received FDA approval for cancer treatment so far. The most widely used include trastuzumab (breast and stomach cancers), bevacizumab (many cancers, particularly colorectal, brain, ovarian, cervical and lung cancers) and rituximab (in some lymphomas and leukemias).

A chimeric monoclonal antibody used in treating non-Hodgkin lymphoma and chronic lymphocytic leukemia, Rituximab (rituximab = trade name Maphtera), exerts its anticancer effect by binding to the CD20 protein on lymphoma and leukemia cell surfaces. CD20 is a protein antigen found on the surface of B-type immune cells. Although CD20’s precise function is unknown, it is thought responsible for calcium uptake into cells and maintaining calcium concentration. It is much more abundant on some B-cell lymphoma and leukemia cells than on normal cells. CD20 antigen, used in both diagnosing these cancers and planning treatment, is a tumor marker (biomarker).

Rituximab binds target cancer cells and activates immune cells known as natural killer (NK) cells. NK cells destroy cancer cells through antibody-dependent mechanisms. Cytokines released from immune cells and substances released by cancer cell destruction attract more immune cells and increase vascular permeability, facilitating drug passage into the tumor. Rituximab also causes certain changes in cancer cells, triggering programmed cell death, apoptosis .

Beyond cancer, rituximab is also used in rheumatoid arthritis, Wegener granulomatosis and microscopic polyangiitis, where suppression of an overactive immune system is desired.