Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts

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Abstract
Background The oncosuppressive properties of some autonomous parvoviruses such as H‐1 virus, together with their low pathogenicity, make them attractive vectors for tumor‐directed gene therapy. Indeed, it was recently shown that these viruses became endowed with an enhanced oncosuppressive activity after they had been engineered to deliver a recognized therapeutic transgene. This prompted us to use a parvoviral vector to analyse the antineoplastic capacity of MCP‐3 (monocyte chemotactic protein‐3), a CC chemokine which has a broad spectrum of target cells, and can thus be considered to be a promising candidate for cancer treatment. Methods We explored the use of a parvovirus H‐1‐based vector encoding human MCP‐3 for its antitumor potential on human cervical carcinoma cells. HeLa cells were infected in vitro with the recombinant virus hH1/MCP‐3 at a low multiplicity [1 replication unit (RU)/cell] and we investigated the effect of parvovirus‐mediated MCP‐3 transduction on tumor formation and growth upon implantation of HeLa cells in nude mice. Results Infection of HeLa cells with hH1/MCP‐3 led to secretion of high levels of MCP‐3 and to significant retardation of tumor growth in recipient mice, as compared with HeLa cells that were either buffer‐treated or infected with a MCP‐3‐free vector. Tumors from hH1/MCP‐3–infected HeLa cells were heavily infiltrated with activated macrophages and showed increased numbers of dendritic cells. In addition, activated natural killer (NK) cells were also recruited into MCP‐3‐transduced tumors. Conclusion These observations indicate that parvovirus H‐1‐transduced MCP‐3 is able to exert a significant antitumor activity which is mediated, at least in part, through macrophages and NK cells, under conditions in which activated T cells are lacking. Copyright © 2001 John Wiley & Sons, Ltd.