Bivalent and Bispecific Monoclonal Antibodies in Cancer Therapy

Bivalent and Bispecific Monoclonal Antibodies in Cancer Therapy 

Bivalent and bispecific monoclonal antibodies have many practical applications, including immunodiagnosis and immunotherapy. Bivalency can allow antibodies to bind 

Because many potentially useful monoclonal antibodies do not possess the appropriate isotype and so are unable to activate human complement and/or trigger Fc-yR on human cells, treatment strategies are needed. One such strategy is the application of bispecific monoclonal antibodies that exploit the specificity of monoclonal antibody and ensure activation of cellular cytotoxic mechanisms (Fanger et al., 1993). 

Bispecific monoclonal antibodies are artificially developed antibodies with antigenbinding sites physically linked to different specificities. It is thought that bispecific monoclonal antibodies activate the cellular immune response by crosslinking immune cells to tumor cells, thus circumventing the proper structures for tumor cell-immune cell interactions (Koelemij et al., 1999). These antibodies are effective in low concentrations in vivo. For example, Kufer et al. (1996) have combined the anti-CD3 specificity directed against T cells in a bispecific monoclonal antibody, with the specificity against the tumor-associated 17-1A antigen. This antibody could be a major improvement, for example, in the therapy for disseminated micrometastatic tumor cells. 

Bispecific monoclonal antibodies are being evaluated in phase I and II studies in a variety of malignant diseases in the fields of hematooncology and solid tumors. It is likely that in the next decade immunotherapy using bispecific monoclonal antibodies will have a place, complementary to the current modalities such as surgery, chemotherapy, hormone therapy, and radiation, in the treatment of malignancies. 

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