Immuno-Isolation in Oncology - A Mini-Review

Pasquale      Cirone; Robert   M.   Saller; Patricia   L.   Chang

Abstract

Immuno-isolation provides a potentially safe and effective method of delivering recombinant therapeutic molecules. Its application as a drug-delivery platform for the treatment of cancer has shown promising developments recently. This review will summarize the principle and current progress of this novel therapy paradigm in oncology. In this approach, a non-autologous cell line is genetically modified to secrete a recombinant product with potential for tumor suppression. Such a cell line may be implanted without graft rejection into all patients with similar neoplastic disease. The immune protection is conferred by enclosure within immuno-isolating devices such as microcapsules whose permeability would allow passage of smaller molecules such as oxygen, nutrients and waste products as well as the desired therapeutic transgene product. However, large immune mediators such as complement, macrophages and lymphocytes responsible for graft rejection would be excluded. In this review, we will consider how t his technology may be applied as a novel genetic tool for cancer treatment to deliver antibodies, cytokines, enzymes and growth factors for treatment of various types of cancer. These molecules can be delivered at low constitutive levels, thereby permitting long-term systemic delivery, maintaining biological activity over extended periods, and eliminating the costs of product purification. The current success of this strategy in cancer treatment will be reviewed in in vitro systems, in animal models of cancer, and in human clinical trials.

Keywords: immuno-isolation, recomninant therapeutic molecules, cancer therapy, immunotherapy, cytokine, anti-angiogenesis, anti-angiogeneic factors, endostain, toxic metabolites, proteolytic enzyme inhibitors