Methods for targeting biologicals to specific disease sites.
Cytokines are mediators of cell communication. Their therapeutic use requires frequent high doses to achieve effective local biological levels. However, the clinical use of some cytokines is limited because of their pleiotropism, which can result in unwanted side effects. Here, we review novel protein engineering technologies that overcome these limitations and enable the targeting of cytokines to specific sites. One such technology uses antibody-based recognition to direct the cytokine to a particular tissue, and another creates encapsulated latent cytokines that are released only at the site of disease. The latter method requires the overexpression of matrix-metalloproteinases, thereby exploiting the severity of the pathological process to regulate drug delivery. Because these technologies are based on the expression of fusion proteins, their application can be extended to other biologicals and can be delivered by gene therapy.
Nissim
Ahuva
A
Bone and Joint Research Unit, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, Charterhouse Square, London EC1M 6BQ, UK.
Gofur
Yarunnessa
Y
Vessillier
Sandrine
S
Adams
Gill
G
Chernajovsky
Yuti
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000503:physiopathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000503:physiopathology / Q000628:therapy; D002450:Cell Communication / Q000502:physiology; D003141:Communicable Diseases / Q000503:physiopathology / Q000628:therapy; D016207:Cytokines / Q000235:genetics / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004337:Drug Carriers; D011993:Recombinant Fusion Proteins; D045726:Metalloproteases