Abstract
Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin’s Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come.
Highlights
Cancer remains the second leading cause of death in the United States, with lung cancer being the leading cause of cancer deaths, followed by breast cancer in women and prostate cancer in men (Siegel 2017)
A genetically engineered chimeric antibody against the Cluster of Differentiation (CD) 20 antigen found on the surface of B cells, was the first monoclonal antibody approved by the Food and Drug Administration in 1997 for the treatment of Non-Hodgkin’s lymphoma (Leget and Czuczman 1998; White et al 2000)
Catumaxomab is a trifunctional antibody produced by a rat-mouse quadroma cell with affinities to CD3 antigen on cytotoxic T cells and epithelial cell adhesion molecule (EpCAM) which is a type 1 transmembrane glycoprotein associated with malignant ascites and effusions and expressed on the majority of epithelial cancers (Linke et al 2010; Seimetz 2011)
Summary
Cancer remains the second leading cause of death in the United States, with lung cancer being the leading cause of cancer deaths, followed by breast cancer in women and prostate cancer in men (Siegel 2017). These bispecific antibodies are divided into two major classes: IgG like bispecific antibodies which carry an Fc region and retain Fc-mediated effector functions and the non-IgG like formats which rely entirely on their antigen binding capacity to exert therapeutic effects. Recombinant techniques have led to the creation of small fragment molecules by combining single chain variable fragments from two different monoclonal antibodies to form bivalent bispecific “antibodies” ranging in size from 50 to 60 kDa (Kontermann 2012) Some examples of these are the bispecific T cell engager (BiTE), tandem single chain variable fragments (taFvs), diabodies (Dbs), single chain diabodies (scDbs), and triplebodies. In the case of T-cells, the target site for binding is
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