Monoclonal antibodies for the therapy of cancer

Abstract

The introduction of monoclonal antibodies for the treatment of cancer Monoclonal Antibodies (mAbs) comprise a class of therapeutic biologics that has been increasingly used over the last decades. The concept of using antibodies to selectively target tumors was proposed by Paul Ehrlich over a century ago [1]. The development of the hybridoma technology in 1975 enabled the production of monoclonal antibodies, which contain uniform variable regions and are thus specific for a single epitope. They are immunoglobulin molecules secreted from a population of identical cells and are homogeneous in structure and binding specificity. Their specificity for the target, together with the fact that they are relatively well tolerated and have a long half-life has contributed to their success in drug development. Antibodies can trigger direct effects on tumor growth causing apoptosis or inhibition of proliferation, they can also mediate immune effector functions. The first antibodies used in the clinic were of murine origin. Due to their immunogenicity in humans and poor ability to induce human immune effector responses, they exhibited limited clinical applicability. Chimeric, humanized and fully human monoclonal antibodies have now been developed to address these problems. Chimeric antibodies are encoded by genes from more than one species, usually with antigen-binding regions from mouse genes and constant regions from human genes, while humanized antibodies are genetically engineered mouse antibody in which the protein sequence has been modified to mimic that of human antibodies [1]. Antibodies can be subdivided into two distinct functional units: the fragment of antigen binding (Fab) and the constant fragment (Fc). The Fab contains the variable region, which consists of three hypervariable complementarity-determining regions (CDRs) that form the antigen binding site of the antibody and confer antigen specificity. The Fc can bind to immune effector cells and complement that can both mediate antibody directed immune killing.