The broad host range of alphaviruses has made it possible to obtain transgene expression in various cell lines including human tumor cell lines. Using the SFV-LacZ virus for the expression of the ^-galactosidase reporter gene, it was demonstrated that human prostate tumor cell lines such as JCA-1, PPC-1, TSU-PR1, ALVA-1, PC-3, DU-145 and LnCaP could not only be efficiently infected, but that SFV also induced an apoptotic response (29). Moreover, the same apoptotic response has been observed in prostate biopsies from patients transduced ex vivo with SFV-LacZ. In another study, tumor cell lines were infected with SFV vectors carrying a fusion construct of the green fluorescence protein (GFP) and herpes simplex virus thymidine kinase (HSV-rfr) gene, which allowed parallel monitoring of the infection efficency by fluorescence (GFP) and tumor killing (HSV-rfr) after ganciclovir (GCV) administration (30). To simulate in vivo conditions, only low multiplicity of infection (MOI) was applied, which resulted in fairly modest GFP expression. However, the tumor killing was much better than anticipated because of the by-stander effect previously observed for HSV-rt treatment (31). These studies, however, made it clear that the delivery of the therapeutic gene is essential and approaches such as intratumoral injections or improved targeting for systemic delivery are essential.
Was this article helpful?