In vivoanti-tumour activity of recombinant MVM parvoviral vectors carrying the human interleukin-2 cDNA

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Abstract
Background The natural oncotropism and oncotoxicity of vectors derived from the autonomous parvovirus, minute virus of mice (prototype strain) [MVM(p)], combined with the immunotherapeutic properties of cytokine transgenes, make them interesting candidates for cancer gene therapy. Methods The in vivo anti‐tumour activity of a recombinant parvoviral vector, MVM‐IL2, was evaluated in a syngeneic mouse melanoma model that is relatively resistant in vitro to the intrinsic cytotoxicity of wild‐type MVM(p). Results In vitro infection of the K1735 melanoma cells prior to their injection resulted in loss of tumorigenicity in 70% of mice (7/10). Tumour‐free mice were protected against a challenge with non‐infected parental cells. In addition, MVM‐IL2‐infected tumour cells induced an anti‐tumour activity on parental cells injected at a distant location. These non‐infected tumour cells were injected either at the same time or 7 days before the injection of MVM‐IL2‐infected cells. In the latter setting, which mimics a therapeutic model for small tumours, 4/10 mice were still tumour‐free after 4 months. Conclusions Our results show that (i) the MVM‐IL2 parvoviral vector efficiently transduces tumour cells; and (ii) the low multiplicity of infection (MOI = 1) used in our experiments was sufficient to elicit an anti‐tumour effect on distant cells, which supports further studies on this vector as a new tool for cancer gene therapy. Copyright © 2004 John Wiley & Sons, Ltd.
Funding Information
  • Fédération Luxembourgeoise contre le Cancer
  • FNRS, Belgium (FRSM 3.4627.01)