A phase I clinical trial has demonstrated that a two-step gene therapy treatment was safe and effective in 31 patients with recurrent glioblastoma (a stubborn form of brain cancer).

These findings, published in the journal Science Translational Medicine potentially overcomes a major hurdle that has hindered the use of systemically administered interleukin 12 (IL-12)-based regimens.

The therapy boosted the infiltration of immune cells into tumours and showed encouraging preliminary benefits, indicating it has promise as a treatment for patients with this usually fatal disease.

Glioblastoma has several approved treatments, but there are currently no curative options.

Studies have found that interleukin 12 (IL-12) - an anti-tumour molecule - has beneficial effects against cancer, but IL-12 cannot be administered systemically due to its unfavourable safety profile.

In search of a much-needed treatment alternative, E. Antonio Chiocca and colleagues developed an approach that leverages the anticancer benefits of IL-12, while limiting its toxicity.

Their two-step approach (conducted after surgical removal of the tumour) involves injecting the tumour site with a viral vector that delivers the gene for IL-12, followed by oral administration of a drug candidate named veledimex that triggers the production of IL-12.

In a multi centre phase I trial, the regimen boosted IL-12 production in the brains of 31 patients with recurrent glioblastoma while limiting the amount of IL-12 that entered systemic circulation.

Although some patients exhibited serious side effects, they were easily reversed after discontinuing the treatment and were less severe in patients receiving lower doses of veledimex.

Anti-tumour immune cells penetrated the tumour more effectively after treatment, and the scientists saw signs that the therapy may have boosted overall survival.

Patients who received restricted doses of the corticosteroid dexamethasone throughout IL-12 treatment showed greater survival benefits, hinting that limiting corticosteroid use could maximise the benefits of IL-12 treatment and similar immunotherapies.

Source: American Association for the Advancement of Science