A first-in-human trial using an oncolytic herpes virus to treat recurrent glioblastoma uncovers dynamic changes in the immune landscape of the peripheral blood and tumor microenvironment

BostonGene, a leading provider of AI-based molecular and immune profiling solutions, today announced the online publication of the manuscript “Clinical trial links oncolytic immunoactivation to survival in glioblastoma,” in Nature, an international journal publishing peer-reviewed research in all fields of science and technology prioritizing originality, significance, interdisciplinary relevance, timeliness, accessibility, sophistication, and groundbreaking findings.

Glioblastoma (GBM) is one of the most aggressive forms of high-grade gliomas characterized by the worst outcome in terms of survival, with rapid recurrence after neurosurgical resection and chemoradiation. Utilization of immunotherapy for GBM has been challenging due to the scarcity of infiltrating antitumor lymphocytes caused by a highly immunosuppressive or “lymphocyte-depleted” tumor microenvironment (TME). For recurrent GBMs and several other highly immunosuppressive solid cancers, novel treatment modalities capable of activating the immune TME into one more amenable to immunotherapy response are essential for improving patient outcomes.

In this first-in-human phase 1 trial, CAN-3110, an oncolytic herpes virus designed by Antonio Chiocca, MD, PhD, Harvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital and his team, was injected into 41 GBM patients. The results demonstrated a single injection of CAN-3110 activated an antitumor immune response in GBM, inducing defined changes in T cell repertoires and tumor transcriptomic signatures. These findings are evidence that intralesional onolytic viruses can convert the immunosuppressive GBM TME to an immunoactivated state that is more responsive to immunotherapy.

"Our discoveries offer robust human immunological and biological validation for intralesional oncolytic therapies. These treatments hold the promise of reshaping the typically immunosuppressive tumor microenvironment found in solid cancers into one that supports the body's natural defenses against cancer,“ said Dr. Chiocca.

"BostonGene's innovative RNA-seq analytics lent novel insights into the dynamic changes associated with CAN-3110 therapy within the glioblastoma microenvironment," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. “Looking to the future, we are excited at the possibilities of harnessing oncolytic viruses to transform immunosuppressive microenvironments across a range of solid cancer types.”

About BostonGene Corporation

BostonGene has a mission to provide transformative, AI-integrated molecular analytics and biomarker discovery for precision matching of therapies to improve the lives of patients living with cancer and other immune-related diseases. BostonGene’s concierge-service model provides customized client solutions using a multi-omic approach prioritized for real-world impact to optimize standard-of-care therapies, accelerate research and provide cost-effective, measurable data-driven results. BostonGene’s tests reveal key drivers of each patient’s unique disease profile, including an in-depth profile of the immune microenvironment, actionable mutations, biomarkers of response to diverse therapies, and recommended therapies. Through these comprehensive analyses, BostonGene’s tests generate a personalized roadmap for therapeutic decision-making for each patient. For more information, visit BostonGene at http://www.BostonGene.com.

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