Polybodies: Next-generation clinical antibodies

Conventional antibodies [full-length and fragments: F(ab′)₂, fragment antigen-binding (Fab), single-chain variable fragment (scFv), variable heavy domain of heavy chain antibody (VHH)] are monospecific, first-generation antibodies, that have dominated the biopharmaceuticals field. However, protein engineering approaches has led to the advent of the next-generation antibodies (polybodies), which are significant improvement over the conventional antibodies. Polybodies comprise polyspecific and/or polyvalent antibodies that enable a single antibody to target multiple specific antigens simultaneously. Polybodies are superior to first-generation antibodies (more efficacious, broad-spectrum, resistance resilient, customizable, etc.) and provide a cost-effective healthcare solution. This review addresses recent developments in polybodies, highlighting their superiority over conventional antibodies and offering future perspectives to encourage the generation of innovative immunotherapies.