Study shows effectiveness of “novel approach” to treat brain tumor

Glioblastoma is a brain tumor which is among the most lethal and difficult to treat. Now a scientific team has tested in a small clinical trial with 41 patients with cancer recurrent a new gene therapy capable of prolonging survival.

These are still preliminary results – phase 1 trial -, but “exciting” that, according to those responsible, “they give hope” for the next steps in a cancer that is “very resistant” to treatment and whose recurrence is associated with a survival of less than 10 months.

The details of the safety and preliminary efficacy of this new gene therapy, mediated by a virus, are published in the journal Nature and are behind it by scientists from Brigham and Womens Hospital (Boston).

Glioblastoma has an aggressive effect in part due to an environment of immunosuppressive factors that surround the tumor and that allow its growth by preventing the immune system from penetrating it and attacking it, explains Antonio Chiocca, director of the Neurosurgery Department at the aforementioned hospital.

To convert this environment into one susceptible to an immune response, the researchers designed a new oncolytic virus capable of infecting cancer cells and stimulating an antitumor immune response. The “novel approach” was able to prolong the survival of patients.

“This study showed that, with a virus designed by us, we can remodel this ‘immune desert’ and turn it into a pro-inflammatory environment,” summarizes Chiocca.

The phase I trial examined the safety of an oncolytic virus called CAN-3110 – now licensed to the company Candel Therapeutics.

The virus that attacks the cancer is an oncolytic herpes simplex virus, which is the same type of virus used in an approved therapy for the treatment of metastatic melanoma.

Specifically, the researchers designed a version of this that contains a certain gene (ICP34.5) but that is also genetically “scheduled” so as not to attack healthy brain cells.

Overall, the trial demonstrated safety in 41 patients with high-grade gliomas, 32 of them with recurrent glioblastoma. The most serious adverse events were seizures in two participants.

Volunteers who had pre-existing antibodies against the herpes simplex virus, HSV-1, (66% of them) had a mean overall survival of 14.2 months.

The scientists observed markers of several changes in the tumor microenvironment associated with immune activation.

Their hypothesis is that the presence of HSV-1 antibodies triggered a rapid immune response to the virus, attracting more immune cells to the tumor and increasing levels of inflammation in the tumor microenvironment.

They also found an increase in the diversity of the T cell repertoire, suggesting that the virus induces a broad immune response.

“Studies like this show how promising gene therapy – which modifies genetic information – is for treating untreatable diseases.”conclude the authors.