OV therapy increases survival in Glioblastoma (GBM) patientsOctober 18, 2023 - Investigators from Brigham and Women’s Hospital (Boston, MA) reported the results of a Phase I clinical trial evaluating a novel engineered oncolytic herpes virus (oHSV) in patients with high-grade recurrent glioblastoma (rGBM). Findings from the first in human study, involving 41 patients, demonstrated the safety and preliminary efficacy of the novel gene therapy. The results also showed that treatment resulted in prolonged survival among a subgroup of recurrent GBM patients who were immunologically “familiar” with the virus and had pre-exiting viral antibodies.
Glioblastoma is an aggressive form of high-grade glioma (HGG) brain cancer that is notoriously resistant to treatment. Recurrent HGG (rHGG), including rGBM are associated with survival of less than 10 months, the authors wrote.
Overall, the trial demonstrated the safety of CAN-3110 in 41 patients with high-grade gliomas, including 32 with recurrent GBM. Notably, GBM participants who had pre-existing antibodies to HSV1 virus (66% of the patients) had a median overall survival of 14.2 months, compared to 7.8. months for seronegative patients. In patients with pre-existing antibodies, the researchers saw markers of several changes in the tumor microenvironment associated with immune activation. They hypothesized that the presence of HSV1 antibodies resulted in a rapid immune response to the virus, which brought more immune cells to the tumor and increased the levels of inflammation in the tumor microenvironment.
The authors also observed an increase in diversity of the T cell repertoire after CAN-3110 treatment, suggesting that the virus induces a broad immune response, perhaps by eliminating tumor cells resulting in the release of cancer antigens. “In summary, single-timepoint intralesional injection of rHGG/rGBM with CAN-3110 enriches the tumor microenvironment with TILs [tumor infiltrating lymphocytes], inducing defined changes in peripheral and tumor T cell repertoires and tumor transcriptomic signatures,” the team commented in their discussion.
“Almost no immunotherapies for GBM have been able to increase immune infiltration to these tumors, but the virus studied here provoked a very reactive immune response with infiltration of tumor-killing T-cells,” Chiocca said. “That’s hard to do with GBM, so our findings are exciting and give us hope for our next steps.”
[All similar to what ONCYs pelareorep has demonstrated ]
https://www.genengnews.com/topics/cancer/oncolytic-virus-therapy-shows-promise-against-glioblastoma-in-first-human-trial/