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

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.

• Authors: K Wetzel, P Menten, G Opdënakker, J Van Damme, H J Gröne, N Giese, A Vecchi, S Sozzani, J J Cornelis, J Rommelaere, C Dinsart
• Journal: The journal of gene medicine (J Gene Med) 2001 Jul-Aug Vol. 3 Issue 4 Pg. 326-37 ISSN: 1099-498X [Print] England
• PMID: 11529662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL7 protein, human
• Ccl7 protein, mouse
• Chemokine CCL7
• Cytokines
• Monocyte Chemoattractant Proteins
• Recombinant Proteins

Topics

• Animals
• Chemokine CCL7
• Cytokines
• Female
• HeLa Cells
• Humans
• Mice
• Mice, Nude
• Monocyte Chemoattractant Proteins (genetics, pharmacokinetics, therapeutic use)
• Parvovirus (genetics)
• Plasmids
• Recombinant Proteins (analysis)
• Transcription, Genetic
• Transduction, Genetic
• Transplantation, Heterologous
• Uterine Cervical Neoplasms (therapy)