Replies to post #74833 on Biotech Values

[genisi]

From Science perspectives on the the two-in-one designer antibodies - Paul W. H. I. Parren and Dennis R. Burton:

Approaches to generate antibody molecules with multiple binding moieties have been tried before, with varying success. Such molecules were engineered by “fusing” two or more antibody binding sites into a single molecule to increase binding avidity or bind multiple antigens. Antibodies binding two antigens can also be generated by Fab arm exchange, which occurs naturally in vivo for immunoglobulin G4 molecules, or can be created in vitro by cell fusion or antibody engineering. Antibodies in which two binding sites recognizing distinct antigens are connected to a single Fab arm represent another permutation. An example that is perhaps the closest comparable break with the one antibody–one antigen dogma comes from chemically programmed antibodies in which antigen recognition is modified by the insertion of different ligands into the antibody binding site via a common reactive group. The beauty of the two-in-one molecule created by Bostrom et al. is its simplicity. For the first time, dual specificity has been engineered into a naturally occurring and stable antibody isotype that should pose no obstacles for manufacturing and that has been well validated for clinical use. ...The uniqueness of the work of Bostrom et al. is to show that promiscuous binding of antibodies is compatible with the high-affinity, pharmacologically relevant, binding of very different antigens. Promiscuous binding may even extend to natural immunity where it would represent a mechanism to maximally cover binding space by a given repertoire of antibodies.

Others are also trying and this work is basic research, but Genentech is one of the few that can succeed, imo.