Antibodies in Single-Chain Format Against Tumour-Associated Antigens:Present and Future Applications

L.      Accardi; P.      Di Bonito

Abstract

The recombinant antibodies in single-chain format (scFv) have found broad applications in both therapeutic and diagnostic fields. Tumour-associated antigens (TAAs) are proteins or other molecular species expressed in a specific tumour type, that can be targeted for diagnostic and immunotherapy purposes. The possibility of obtaining highly selective and efficacious scFvs makes them appropriate tools to target TAAs. The approach utilised for targeting depends on the nature of TAAs and their cell localisation. Tumour antigens displayed on the cell surface can be recognised by scFvs coupled to radioisotopes, toxins and enzymes to be used in cancer diagnosis and therapy. Intracellular tumour antigens can be targeted by scFvs expressed as “intracellular antibodies”. This review reports the existing scFv-based formats, hints of their generation and pharmacokinetics, and a description of the most promising TAAs. It also provides an update of in vitro, preclinical and clinical studies using scFvs against TAAs for cancer diagnosis and treatment, with their merits and limits.

Keywords: Single-chain antibody fragments, tumour-associated antigens, recombinant antibodies, intrabodies, cancer diagnosis, cancer therapy, targeted immunotherapy