Latent cytokines for targeted therapy of inflammatory disorders.

Introduction: The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules.

Latency can be conferred to a variety of cytokines by fusion with latency-associated peptide from TGF-β.

Objectives: Targeting cytokines to sites of disease has clear advantages because it increases their therapeutic index. We designed fusion proteins of the latent-associated peptide (LAP) derived from TGF-β with various cytokines via a matrix metalloproteinase (MMP) cleavage site. This design confers latency, increased half-life and targeting to sites of inflammation.

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

Background: Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site.

Objectives: To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release.

Methods: Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays.

Research to combat urinary incontinence.

In this article, brought to you in association with Help the Aged, the authors discuss current research into the causes and management of urinary incontinence.

Fighting cancer with oncolytic viruses.

Although gene therapy has huge potential for modern medicine, our enthusiasm for its powerful potential must not cloud our judgment about the dangers of using increasingly diverse, yet relatively untested, replicating viruses