Characterization of human mesothelioma cell lines as tumor models for suicide gene therapy.
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.


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.


CONCLUSIONS
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.
Veldwijk
Marlon R
MR
Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Berlinghoff
Simone
S
Jauch
Anna
A
Laufs
Stephanie
S
Zeller
W Jens
WJ
Wenz
Frederik
F
Fruehauf
Stefan
S
D000818:Animals; D045744:Cell Line, Tumor; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D008654:Mesothelioma / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D014161:Transduction, Genetic / Q000379:methods*