Polybodies: Next-generation clinical antibodies

[Display omitted] •Full-length antibody and antibody fragments are first-generation conventional Mabs.•Protein engineering enables development of the next-generation polybody.•The polybody is a polyspecific and polyvalent antibody.•Polybodies bind to multiple specific antigens simultaneously.•The polybody is more efficacious, broad-spectrum, cost-effective, etc. 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.