Biomarker Analysis Identifies Predictors of Long-Term Survival in Glioblastoma Patients Receiving SurVaxM Immunotherapy
核心洞察
Researchers at Roswell Park identified tumor biomarkers that predict which glioblastoma (搜索) patients will achieve long-term survival when treated with SurVaxM immunotherapy.
Long-term survivors showed high proportions of B cells and T cells in their tumors, along with enriched interferon-gamma and interferon-alpha gene sets.
A five-gene expression signature and B-cell-specific signature predicted survival length in SurVaxM-treated patients but not in those receiving standard treatment alone.
Researchers at Roswell Park Comprehensive Cancer Center have identified specific tumor biomarkers that can predict which glioblastoma (搜索) patients are most likely to achieve long-term survival when treated with the investigational immunotherapy SurVaxM. The findings, published in Cancer Immunology & Immunotherapy, could help clinicians identify patients who would benefit most from this therapeutic approach.
The study analyzed data from a single-arm phase 2 clinical trial involving 63 newly diagnosed glioblastoma (搜索) patients who received standard treatment—surgery, chemoradiation, and temozolomide chemotherapy—followed by SurVaxM injections. Using whole-exome and RNA sequencing, investigators examined the molecular characteristics of pre-treatment tumors from 34 patients.
Immune Cell Infiltration Linked to Survival
The analysis revealed that patients with long-term survival (more than 18 months) had tumors containing significantly higher proportions of B cells and T cells compared to short-term survivors (fewer than 18 months). These immune cells form part of the body's cancer-killing arsenal and appear crucial for the immunotherapy's effectiveness.
"Our findings suggest that analyzing patients' tumors before treatment could help us identify those who would be most likely to benefit from SurVaxM or other types of immunotherapies," said Michael Ciesielski, Ph.D., Assistant Professor of Neurosurgery and Director of the Neuro-Oncology Lab at Roswell Park, who co-developed SurVaxM with Robert Fenstermaker, MD.
Interferon Signatures Predict Response
Long-term survivors also showed enriched gene sets for interferon-gamma (IFN-γ) and interferon-alpha (IFN-α), proteins that help the immune system mount stronger attacks against tumors. The researchers identified a five-gene expression signature and B-cell-specific signature that predicted survival length in SurVaxM-treated patients.
Importantly, these same tumor characteristics were not associated with improved survival in patients who received similar standard treatment without immunotherapy, suggesting the biomarkers are specifically predictive of immunotherapy response rather than general prognostic factors.
SurVaxM Mechanism and Clinical Impact
SurVaxM targets survivin (搜索), a protein found in 95% of glioblastomas that is essential for tumor survival. The immunotherapy works by stimulating patients' immune systems to find and destroy cells containing survivin, potentially preventing disease recurrence.
The clinical impact has been substantial for some patients. Ten patients have survived seven years or longer after receiving SurVaxM, including five whose disease has not recurred. This represents a significant achievement given that glioblastoma (搜索) is the most common, aggressive, and deadly type of brain tumor (搜索), with fewer than 7% of patients surviving five years after diagnosis.
Addressing Critical Medical Need
"There is an urgent need for more effective treatments for glioblastoma (搜索), which claims about 10,000 lives in the U.S. every year," Ciesielski noted. The identification of predictive biomarkers could help optimize patient selection for immunotherapy trials and improve treatment outcomes.
Broader Applications
Because survivin (搜索) is present in many other cancers, SurVaxM is being evaluated in clinical trials for adult patients with neuroendocrine tumors (搜索) and multiple myeloma (搜索), as well as pediatric patients with specific brain tumors. The biomarker findings may have implications for these other cancer types as well.
The research was supported by grants from the Roswell Park Alliance Foundation, Philip H. Hubbell, the Linda Scime Endowment, MimiVax Inc (搜索)., and National Institutes of Health awards. The study included collaborators from multiple institutions including Miami Cancer Institute, Dana-Farber Cancer Institute, Massachusetts General Hospital Cancer Center, and Cleveland Clinic Neurological Institute.