Development of chemokine-expressing retrovirus vector system in malignant gliomas

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The C-C chemokines including such molecules as MIP-1alpha (macrophage inflammatory protein-1 alpha) and MCAF (monocyte chemotactic and activity factor) exhibit chemoattractant potential for monocytes and T lymphocytes. We have developed retrovirus and adenovirus vector system which allow expression of the C-C chemokines to evaluate the effect of localized secretion of the chemokines on host anti-tumor response in rat given subcutaneous innoculation of 9L gliosarcoma cells followed by virus injection in vivio. The production of MIP-1alpha by infected adenovirus did not influence the growth rate in vitro, but suppressed tumor growth when the virus is injected into 9L flank tumor of F344 rats. Histological examination of the site of injection of 9L injected with MIP-1alpha expressing adenovirus vector showed predominantly T cell infiltration. These results indicated that chemokines have potent anti-tumor activities when released at the tumor site. Our studies highlight the potential usefulness of localized chemokine secretion in inducing potent antitumor host responses.