Monoclonal antibodies: versatile platforms for cancer immunotherapy

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Abstract
The past century has witnessed the evolution of the 'magic bullet' from concept to clinical reality. Therapeutic antibodies have been established as 'standard of care' agents for several human cancers. Therapeutic antibodies possess unique and multiple clinically relevant antitumour mechanisms: these include antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and the induction of T cell immunity through cross-presentation. Antibodies directed against elements of the tumour microenvironment might synergize with antibodies targeting tumour antigens and provide enhanced therapeutic benefit. Fc receptors for IgG (FcγRs) provide a key link between therapeutic antibodies and the cellular immune system and enable monoclonal antibodies to induce adaptive immune responses. Antibody-induced antitumour adaptive immunity against tumour-specific antigens might already contribute to the patterns of delayed and prolonged antitumour responses seen when antibodies are used alone or in combination with chemotherapy. Monoclonal antibodies can exert synergistic antitumour effects in combination with other immunomodulatory approaches such as chemotherapy, radiotherapy, targeted therapy agents, vaccines or other immunomodulators. Advances in protein engineering have provided platforms for the development of novel antibody constructs, such as bispecific T cell engager (BiTE) molecules, as well as engineered protein scaffolds, such as designed ankyrin repeat domains (DARPins) and adnectins.