In vivo anti-tumour activity of recombinant MVM parvoviral vectors carrying the human interleukin-2 cDNA.
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.
El Bakkouri
Karim
K
IBMM-IRIBHM, Université Libre de Bruxelles, rue des professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
Servais
Charlotte
C
Clément
Nathalie
N
Cheong
Siew Chiat
SC
Franssen
Jean-Denis
JD
Velu
Thierry
T
Brandenburger
Annick
A
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008915:Minute Virus of Mice; D014161:Transduction, Genetic / Q000379:methods
D007376:Interleukin-2