Virus-Based Therapy Boosts Anti-Cancer Immune Responses to Brain Cancer

A team led by investigators at Mass General Brigham and Dana-Farber Cancer Institute has shown that a single injection of an oncolytic virus—a genetically modified virus that selectively infects and destroys cancer cells—can recruit immune cells to penetrate and persist deep within brain tumors. The research, which is published in Cell, provides details on how this therapy prolonged survival in patients with glioblastoma, the most common and malignant primary brain tumor, in a recent clinical trial. 

“Patients with glioblastoma have not benefited from immunotherapies that have transformed patient care in other cancer types such as melanoma because glioblastoma is a 'cold' tumor with poor infiltration by cancer-fighting immune cells,” said co-senior author Kai Wucherpfennig, MD, PhD, chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute. “Findings from our clinical trial and our mechanistic study show that is now feasible to bring these critical immune cells into glioblastoma.”

The oncolytic virus used in the team’s trial, which was developed by E. Antonio Chiocca, MD, PhD, Executive Director of the Center for Tumors of the Nervous System at Mass General Brigham Cancer Institute, is made from a herpes simplex virus genetically altered so it can only make copies of itself in glioblastoma cells and not normal healthy cells. The virus spreads to a glioblastoma cell, kills it, and then makes a copy of itself that spreads again to another glioblastoma cell. Infection of cells with the virus also triggers an immune response. In the phase 1 trial of 41 patients with recurrent glioblastoma, the oncolytic virus treatment extended survival compared to historically reported survival, especially among those with pre-existing viral antibodies.

In their Cell study, the investigators examined the extent of this immune response in clinical trial participants. Their analysis revealed that the treatment induced long-term infiltration of immune T cells into patients’ tumors. Closer proximity of cytotoxic T cells with dying brain tumor cells was associated with longer patient survival after treatment. The therapy also expanded pre-existing T cells in the brain.

“We show that increased infiltration of T cells that are attacking tumor cells translates into a therapeutic benefit for patients with glioblastoma,” said Chiocca, who is also a co-senior author of the study. “Our findings could have important implications for a cancer whose standard of care hasn’t changed for 20 years.”

Authorship: In addition to Wucherpfennig and Chiocca, authors include Maxime Meylan, Ye Tian, Lijian Wu, Alexander L. Ling, Daniel Kovarsky, Graham L. Barlow, Linh D. Nguyen, Jason Pyrdol, Sascha Marx, Lucas Westphal, Julius Michel, L. Nicolas Gonzalez Castro, Sydney Dumont, Andres Santos, Itay Tirosh, and Mario L. Suva.

Disclosures: Wucherpfennig serves on the scientific advisory boards of DEM BioPharma, Solu Therapeutics, D2M Biotherapeutics, DoriNano, Inc., and Nextechinvest; is a co-founder of Immunitas Therapeutics; receives sponsored research funding from Fate Therapeutics; and holds equity in TScan Therapeutics. These activities are not related to the research reported in this publication. Suva is a scientific co-founder and advisory board member of Immunitas Therapeutics. Chiocca is an advisor to Bionaut Labs, Seneca Therapeutics, Calidi Biotherapeutics, and ReIgnite Therapeutics; has equity options in Bionaut Laboratories, ReIgnite Therapeutics, Seneca Therapeutics, and Ternalys Therapeutics; and is co-founder and on the board of directors of Ternalys Therapeutics. Patents related to oHSV and CAN-3110 are under the possession of Brigham and Women’s Hospital with Chiocca, and he is named as co-inventor. These patents have been licensed to Candel Therapeutics. Present and future milestone license fees and future royalty fees are distributed to Brigham and Women’s Hospital from Candel.

Funding: This work was supported by National Cancer Institute (NCI) grants P01 CA236749, P01 CA163222, R01 CA238039, R01 CA251599, P01 CA163205 and R01 NS110942. Meylan is a Cancer Research Institute Immuno-Informatics Fellow supported by the Cancer Research Institute (CRI award #CRI5000) and received mobility grants from l’Institut Servier (CT0101954) and the Philippe Foundation.

Paper cited: Meylan M et al. “Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial” Cell DOI: 10.1016/j.cell.2025.12.055