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

✍ Scribed by Karim El Bakkouri; Charlotte Servais; Nathalie Clément; Siew Chiat Cheong; Jean-Denis Franssen; Thierry Velu; Annick Brandenburger

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 153 KB
• Volume: 7
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.653

✦ Synopsis

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 new tool for cancer gene therapy.