Ark's 'study 904', which was approved by the UK Gene Therapy Advisory Committee in 2004, randomized 236 people with brain cancer to receive Cerepro plus standard care or standard care alone, which consists either of surgery and radiotherapy or of surgery and radiotherapy plus the alkylating drug Temodar/Temodal (temozolomide) from Schering-Plough in Kenilworth, New Jersey. Subjects given Cerepro and temozolomide showed a 42-day improvement over standard care in median survival, reaching significance (P < 0.032). Side effects hemiparesis, aphasia and pyrexia could be blamed on ganciclovir, which is part of the Cerepro protocol and is “pretty toxic,” says analyst Stephen Dunn of Boca Raton, Florida–based securities firm Dawson James.
The data, due for a full airing at the European Association of Neuro-Oncology in Barcelona as Nature Biotechnology went to press, seem strong. Cerepro—which consists of the herpes simplex virus gene for thymidine kinase (TK) encased in an adenoviral vector in which the E1 and part of the E3 regions have been deleted to prevent replication—was tested in people with operable, high-grade malignant glioma. Doctors injected Cerepro into the cavity left by the removed tumor during the surgery. In the following days, physicians administered ganciclovir—Basel, Switzerland-based Roche's approved drug for cytomegalovirus (sold under the brand names Cytovene and Cymevene). The transformed cells expressing TK convert the prodrug ganciclovir into highly toxic deoxyguanosine triphosphate, which kills any remaining cancer cells. “All the TK does is provide a target for a second drug,” says Dunn. “It's an interesting way of doing it, and safe.”
This is a preview of subscription content, access via your institution