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.