MCP-3 (CCL7) delivered by parvovirus MVMp reduces tumorigenicity of mouse melanoma cells through activation of T lymphocytes and NK cells

Monocyte chemotactic protein 3 (MCP-3/CCL7), a CC chemokine able to attract and activate a large panel of leukocytes including natural killer cells and T lymphocytes, could be beneficial in antitumor therapy. Vectors were constructed based on the autonomous parvovirus minute virus of mice (MVMp), carrying the human (MCP-3) cDNA. These vectors were subsequently evaluated in the poorly immunogenic mouse melanoma model B78/ H1. The infection of the tumor cells with MCP3-transducing vector at low virus input multiplicities, but not with wild-type virus, strongly inhibited tumor growth after implantation in euthymic mice. In a therapeutic B78/H1 model, repeated intratumoral injections of MCP3-tranducing virus prevented further tumor expansion as long as the treatment was pursued. The antitumor effects of the MCP-3-transducing vector were not restricted to this tumor model since they could also be observed in the K1735 melanoma. The depletion of CD4, CD8, NK cells and of interferon γ (IFNγ) in mice implanted with MVMp/MCP3-infected B78/H1 cells abolished the antitumor activity of the vector. The latter data, together with tumor growth in nude mice and reverse-transcriptase (RT)-PCR analyses of MVMp/MCP3-treated tumors, clearly showed that activated CD4, CD8 and NK cells were indispensable for the antineoplastic effect in the B78/H1 tumor. Altogether, our results show that MCP3-transducing parvovirus vectors may be quite potent against poorly or nonimmunogenic tumors, even in conditions where only a fraction of the tumor cell population is efficiently infected with recombinant parvoviruses.