Intra Tumoral Delivery of Viral Vectors or Slowrelease Systems

Viral vectors have been very useful for intra-tumoral application of GM-CSF or CCL16 chemokine in combination with anti-IL-10 and CpG. Introduction of aden-oviral vector expressing CD40 L into a murine bladder cancer caused the downreg-ulation of IL-10 and TGF-a and a 200-fold upregulation of IL-12 combined with small tumor regression [112]. Direct intra-tumoral injection of viral vectors may only serve as proof of concept. For clinical application it seems appropriate to develop agents that can be delivered systemically to target tumor metastases. Such agents could be recombinant viruses with substituted ligands that target tumor expressed receptors or it could be antibody constructs that selectively recognize tumor markers and which are complexed with specific chemokines.

Another concept of changing the tumor micro-environment is via introduction of slow release cytokine depots. This has been shown with IL-2 gels composed of poly-N-acetylglucosamine-polymers. In malignant mesothelioma this caused the triggering of inflammation and of infiltrating CD8 T cells [113]. Tumor endothelia can be influenced via the secretion of interferon-y and this has been shown to cause the largest number of gene expression changes in endothe-lia [114].

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