Bispecific antibodies development

Shalaby, M.R., Shepard, H.M., Presta, L., et al. (1992). Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells over expressing the HER2 proto-oncogene. J. Exp. Med., 175, 217-225. 

This chapter describes the procedures developed in the laboratory of Martin Glennie at the Lymphoma Research Unit, Tenovus Laboratory, Southampton, UK, for preparing bispecific F(ab)2 and F(ab)3 and tnspecific antibody (TsAb) F(ab)3 derivatives from antibody Fab fragments using the crosslinker o-phenylenedi-maleimide (o-PDM)... 

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. 

There are several relatively new therapeutic modalities for the treatment of SLE. Trying to eliminate pathogenic anti-dsDNAs, Ferguson etal. developed an antigen-based heteropolymer (AHP) (F3). AHP is a bispecific dsDNA x monoclonal antibody (mAb) complex (dsDNA x anti-CRl mAb) that enables the use of the unique immune complex-binding and clearing capacity of the complement receptor (CR1) on primate erythrocytes. In vitro studies of AHP show a substantial reduction (>90%) of anti-dsDNA titer (F20). In vivo studies in two rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation (F3). 

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