HSV1716 persistence in primary human glioma cells in vitro

HSV1716 is a selectively replication competent mutant of herpes simplex virus which is in trial in glioma patients. We have demonstrated that HSV1716 is non-toxic when delivered into tumour or into brain adjacent to tumour, yet replicates within tumour cells. Tumour tissue, from one patient treated 2.5 years previously with intra-tumoural HSV1716, was put into culture. The cultured cells were shown to be glial in origin with no evidence of residual HSV1716. These cells were subsequently infected at a MOI of 0.1 with either HSV1716 or wild-type HSV17(+). The HSV17(+) infected cells were completely rounded up or lysed within 72 h. Although the cells supported HSV1716 replication and also became rounded or lysed, a proportion (approximately 20%) remained viable. These cells continued to divide and shed low levels of HSV1716 up to 31 days after infection when there was evidence of rapid virus replication resulting in complete cell lysis. These data demonstrate that HSV1716 can 'persist' in human glioma cells at least in vitro and gives credence to the possibility that in tumours in vivo a similar phenomenon may take place. If this were the case, then HSV1716 has the potential to kill tumour cells over a prolonged period of time.