Monoclonal antibodies in the treatment of acute lymphoblastic leukemias

Abstract

Several monoclonal antibody-based agents have potential application in the treatment of acute lymphoblastic leukemia (ALL) and bring the promise of increased response rates without excessive toxicity. These include unconjugated monoclonal antibodies, monoclonal antibodies or fragments linked to cytotoxic agents or conjugated to toxins (immunotoxins), bispecific single-chain antibodies that redirect cytotoxic T lymphocytes (via CD3 expression) to surface ALL antigens (eg. CD19) and bispecific T-cell engagers.

Monoclonal antibody-based reagents react with blasts by direct and/or indirect mechanisms. Binding by unconjugated monoclonal antibodies directly induce cytotoxicity through inhibition of proliferation or triggering of cell death pathways. Indirect killing may occur via antibody-dependent cell-mediated cytotoxicity and/or complement-dependent cytotoxicity. The cytotoxicity of monoclonal antibodies can increase by linkage to chemotherapy agents and bacterial toxins therefore they do not require active immune response mechanisms for activity and can be effective even in profoundly immunocompromised patients.

Herein, we will review the results and status of investigational monoclonal antibody-based therapies in ALL.