Novel gene therapy shows preliminary efficacy for glioblastoma
Click Here to Manage Email Alerts
Key takeaways:
- Researchers reported median OS of 14.2 months among patients with preexisting antibodies to HSV1 virus.
- The therapy appeared safe.
A novel oncolytic virus gene therapy extended survival among a small cohort of patients with high-grade glioblastoma, according to study results published in Nature.
CAN-3110 (Candel Therapeutics) also appeared safe, findings from the first-in-human clinical trial showed.
Rationale and methodology
“Glioblastoma is an incurable cancer. Even new immunotherapies that have seen success with a lot of other cancers have failed with glioblastoma,” Ennio Antonio Chiocca, MD, PhD, chair of the department of neurosurgery and co-director of the Institute for the Neurosciences at Brigham and Women’s Hospital, as well as Harvey W. Cushing professor of neurosurgery at Harvard Medical School, told Healio. “A reason for failure is that glioblastoma can escape patients’ own immune cells that actively fight against tumors. In our laboratories, we engineered a tumor selective biologic agent — based on the cold sore virus, herpes simplex virus type 1 — to inject into the glioblastoma of patients with the goal to see if we could reshape the disease to become less able to escape patients’ immune cells.”
Researchers sought to assess the novel CAN-3110 vaccine among 41 patients with high-grade gliomas, including 32 with recurrent glioblastoma.
Investigators hypothesized that the ICP34.5 gene — included in the novel therapy, but often excluded from clinical oncolytic herpes viruses — would be necessary to trigger a robust, pro-inflammatory response required for attacking glioblastoma tumors.
Findings
The therapy appeared safe. Two patients experienced seizures, the most common serious adverse event.
Researchers reported median OS of 14.2 months among the 66% of patients with preexisting antibodies to herpes simplex virus type 1 (HSV1).
Patients with preexisting HSV1 antibodies experienced changes in the tumor microenvironment associated with immune activation, which led the researchers to hypothesize that the presence of HSV1 antibodies resulted in a rapid immune response to the virus that brought more immune cells to the tumor and increased the levels of inflammation in the tumor microenvironment, according to a press release.
Researchers observed an increase in the diversity of the T cell repertoire after treatment with the CAN-3110 therapy, thus indicating that the virus induces a broad immune response, according to the release.
“We showed that this biologic agent does lead to a relatively durable change in glioblastoma, which allows immune cells to activate molecular programs that are typical of those which reject cancer cells,” Chiocca said. “In fact, we showed that this activation was linked to survival responses in patients with glioblastoma.”
Implications
“We have shown that one single timepoint administration of CAN-3110 is sufficient to activate immune anticancer programs and, for the first time, have linked this immunoactivation with patient survival,” Chiocca told Healio.
“With support from the philanthropic foundation Breakthrough Cancer we are now performing multiple timepoint injections of CAN-3110 into patients to longitudinally treat glioblastoma during a 4-month timeframe, as well as sample the cancer being treated to ensure that these immunoactivating programs remain operative,” he said.
References:
- Ling AL, et al. Nature. 2023;doi:10.1038/s41586-023-06623-2.
- Researchers design gene therapy that can effectively target glioblastoma (press release). Available at: https://medicalxpress.com/news/2023-10-gene-therapy-effectively-glioblastoma.html. Published Oct. 18, 2023. Accessed Oct. 18, 2023.
For more information:
Ennio Antonio Chiocca, MD, PhD, can be reached at eachiocca@bwh.harvard.edu.
Collapse
Ling AL, et al. Nature. 2023;doi:10.1038/s41586-023-06623-2.
Read more about
Click Here to Manage Email Alerts