Australian dermatologists use ‘Trojan horse’ virus to deliver interferon within BCCs

Skin cancers

By Mardi Chapman

28 Oct 2020

Intralesional injections of a genetically modified adenovirus carrying human genes which code for gamma interferon are showing promise as a treatment for multiple BCCs.

Dermatologist and principal investigator Dr Greg Siller, from Central Brisbane Dermatology, leads a phase 2 study of the adenovirus combined with the hedgehog pathway inhibitor vismodegib.

Dr Siller told the limbic that there aren’t any non-surgical options for nodular or naevoid BCC.

“Unfortunately the topical therapies which are available are suitable and useful for superficial BCC but not nodular BCC and they are not suitable for patients with Gorlin syndrome because the tumour bulk is just too much.”

“So the only thing we have previously been able to offer those people is early diagnosis and small operations. There was a desperate need particularly in patients with multiple BCCs who have suffered the disfigurement of multiple surgeries.”

He said the adenovirus was being used as a Trojan horse to get interferon into the tumour cells.

“Interferon is an important cytokine with potent anti-tumour effects,” he said.

“The beauty of this delivery system is that not only are we delivering interferon, which we could just inject anyway but it’s very toxic, but we are using the virus to trigger a form of programmed cell death … that presents itself nicely to the immune system.”

He said the pilot study of 20 patients treated with just the loaded adenovirus had a cure rate of 84% at 16 weeks.

“That was very encouraging but we felt we could do a bit better than that. The issue where we are trying to make substantial breakthroughs is not in the management of the individual nodular BCC but in getting non-target tumour effects. We have evidence in the first trial that we had developed some abscopal effect.”

He said the phase 2 trial will go for six months – allowing more time for the treatment to take effect.

“One of the reasons we are confident we have got a better than 84% cure rate is that in the first trial, we excised all of the target tumours at week 16 or 17. Of those who weren’t cured, all of them had ongoing regression.”

“So we think that if we had left it a bit longer we may have got a better cure rate. So this time we are biopsying at 26 weeks.”

Dr Siller said there was also interest in challenging other difficult to treat tumours such as metastatic melanoma with combinations of the adenovirus and therapies such as PD-1 inhibitors.

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