Technology evaluation: DISC.

Cantab is developing its DISC technology as a potential gene therapy product for cancer (DISC-Onc) and neurological and blood disorders (DISC-GT). Clinical trials are expected to commence in early 1999 [296831]. The DISC technology utilizes a herpes virus that has had a gene removed to prevent it from replicating [250526]. Phase I trials in leukemia were scheduled to commence in 1998 [250526], however, it was decided that although DISC-Onc is capable of carrying genes into leukemic cells, the levels of immunomodulator genes did not meet the target initially set for the commencement of trials. Hence, Cantab turned its attention to other cancers, and hoped to identify an alternative target for phase I trials in the first half of 1998 [279798]. Additional preclinical work using a murine version of the lead construct produced a significant therapeutic effect in animal tumor models [289716]. DISC-Onc is envisaged to deliver immunogenic genes such as cytokine or stimulatory protein genes [275129]. Cantab, in collaboration with Nottingham Trent University and Birmingham University, has shown that the DISC-Onc has delivered genes effectively to human colorectal, gastric and ovarian cancer tumors. Transfection rates have been shown to be favorable and have been proven to be at least as good as, if not better than, other vectors [279798]. Also, DISC-Onc carrying a functional GM-CSF, has antitumor activity in mouse models of renal cancer and leukemia [250526], [261768]. The DISC Neurology technology (DISC-GT), for gene therapy of neurological disease, is being developed in collaboration with Cambridge University, and enables HSV-driven long-term gene expression in nerve cells [279798].