Onkologie. 2008 Mar;31(3):91-6. Epub 2008 Feb 8. [Link]
Veldwijk MR, Berlinghoff S, Jauch A, Laufs S, Zeller WJ, Wenz F, Fruehauf S.
Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Background: The median survival time of patients with malignant pleural mesothelioma (MPM) remains poor. Therefore, novel therapeutic options are in high demand, and well characterized model systems for in vitro/vivo screening have to be established.
Material and Methods: For this purpose, 3 MPM cell lines (H-Meso-1, MSTO211H, and NCI-H28) were characterized and tested for susceptibility to recombinant adeno-associated virus 2 (rAAV2)-based vectors which have the potential for a loco-regional application.
Results: Using multiplex fluorescence in situ hybridization, several recurrent chromosomal aberrations were observed for each of the MPM cell lines. Tumorigenicity of H-Meso-1 and MSTO-211H cells was shown in an intraperitoneal NOD/SCID mouse model, whereas NCI-H28 cells did not yield any tumors. Although all 3 cell lines were readily susceptible to rAAV2 vectors, differences in susceptibility were observed (H-Meso-1 > NCI-H28 > MSTO-211H). Furthermore, the efficacy of a potential suicide gene therapy using an rAAV2 suicide vector-transduced MPM cell line was determined in a proof-of-feasibility in vivo experiment.
Conclusion: The characterized cell lines described here may serve as a model for in vitro and in vivo preclinical gene therapy for the treatment of MPM using rAAV2 suicide vectors.
Keywords: Mesothelioma, FISH, Adeno-associated virus, Mouse model, Suicide gene therapy