ABSTRACT

Bispecific antibodies (bsAbs) are immunoglobulin-based molecules that contain two different binding specificities. Of particular interest is the ability of bsAbs to redirect immune effector cells against experimental targets in vitro and against tumors and other unwanted cells in a clinical setting. A number of cytotoxic triggering molecules have been identified in leukocyte populations. The T cell receptor is a multi-chain protein consisting of antigen recognition and signal transducing portions. The simplest way of preparing a bispecific antibody is to chemically crosslink two antibodies using reagents that randomly link the antibodies by amino acid side chain groups, usually e-amino groups on lysine residues. The fusion of two different hybridomas can result in the formation of a stable “hybrid-hybridoma” or “quadroma” line that produces as one of its products a homogeneous bsAb. Homogeneous bsAbs can be formed by crosslinking two different F(ab’) fragments via their hinge sulfhydryl residues.