Researchers from Duke’s Preston Robert Tisch Brain Tumor Center have found that a therapy targeting the epidermal growth factor receptor (EGFR) can be safely delivered directly into recurrent glioblastomas and may improve patient outcomes.
In a paper published in Nature Medicine, researchers tested a therapy called D2C7-ATC, an antibody-toxin conjugate designed to recognize and attack two common forms of EGFR, a protein found on many glioblastoma cells.
The novel treatment is delivered directly into the tumor using convection-enhanced delivery, allowing high concentrations of the drug to reach cancer cells while minimizing exposure to the rest of the body.
Vidyalakshmi Chandramohan, PhD, MBA, the paper’s first author, said the research is especially exciting because investigators found evidence that D2C7-ATC may also stimulate the body’s immune system, triggering inflammatory and immune responses associated with longer survival in some patients.
“This dual mechanism, directly targeting tumor cells while simultaneously activating the immune system, represents a promising new therapeutic strategy for recurrent glioblastoma,” Chandramohan said.
EGFR has been considered one of the most promising therapeutic targets in glioblastoma, but previous treatments directed at the protein have had inconsistent results.
Unexpected insights
Chandramohan said this study found an unexpected biological insight: patients whose tumors had lower baseline EGFR expression experienced overall longer survival following treatment.
“The effectiveness of D2C7-ATC may depend on more than simply the amount of EGFR present in a tumor,” Chandramohan said.
Other aspects of tumor biology, including treatment-induced immune responses, may play an important role in determining outcomes. This could help determine which patients may benefit the most from D2C7-ATC.
If this finding is confirmed in larger studies, the biomarkers could offer valuable direction for future studies aimed at developing effective and personalized glioblastoma treatments.
Developed at Duke
The work on D2C7-ATC went from bench to bedside at Duke. The therapy was developed by Darell Bigner, MD, PhD, and Chandramohan and manufactured by Chandramohan and others in the Bigner Lab at Duke. Annick Desjardins, MD, FRCPC, led the Phase 1 clinical trial. Bigner and Desjardins are co-senior authors on the paper.