Bispecific Antibody Production

The bispecific monoclonal antibody (BsMAb, BsAb) is an artificial antibody protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling, and to stimulate interactions of protein complexes. BsAbs have shown great promises in cancer immunotherapy, drug delivery, and slowing the development of the Alzheimer’s disease.

Recombinant bispecific monoclonal antibodies were previously cloned into mammalian expression vectors, such as pcDNA3.1  and transiently transfected into HEK293 or COS cells for transgenic expression. This approach has three disadvantages – (1) HEK293 cells and COS cells are surrogate cell models that lack endogenous antibody production and secretion machinery as in native B cells; (2) Transient transfection lacks the ability to make stable cell lines that can continuously secrete IgG molecules over many generations of cell culture; (3) Transient transfection is difficult to simultaneously introduce two monoclonal antibody molecules into the same cell to facilitate bispecific antibody assembly.

BiCell Scientific’s bispecific antibody production service harnesses the advantageous lentiviral transduction ability to sequentially introduce two monoclonal antibodies into naive B cell hybridomas. The resultant B cell hybridomas can produce recombinant antibodies at a similar level to native B cell-myeloma fused hybridomas. The two monoclonal antibody molecules carry the “knobs-into-holes” mutations in the Fc domain, which will facilitate their heterodimeric assembly into a functional bispecific antibody.