Repair Assisted Damage Detection (RADD) as a predictive biomarker for immunotherapy response in ovarian cancer

Area of Science:

• Oncology
• Immunotherapy
• Biomarker Discovery

Background:

• Genomic instability is a potential predictive biomarker for immunotherapy in ovarian cancer.
• Assessing DNA damage offers a direct measure of genomic instability.

Purpose of the Study:

• To evaluate DNA damage measurement using Repair Assisted Damage Detection (RADD) as a biomarker for immunotherapy response.
• To assess RADD's ability to predict response to Vigil (gemogenovatucel-T) in ovarian cancer patients.

Main Methods:

• 82 ovarian tumors from the VITAL trial were analyzed using RADD for DNA damage assessment.
• RADD scores were correlated with patient survival, CD39 expression, and gene expression signatures.

Main Results:

• RADD scores predicted HR status and correlated significantly with the biomarker CD39, particularly in HRP tumors.
• High RADD scores indicated worse recurrence-free survival (RFS) in the placebo arm but predicted significantly improved RFS with Vigil maintenance therapy.
• High DNA damage levels were associated with immune evasion proteins.

Conclusions:

• RADD effectively measures DNA repair proficiency without relying on mutation signatures or expression profiling.
• Elevated DNA damage levels identified patients who benefit from Vigil maintenance therapy, suggesting RADD as a novel biomarker for immunotherapy stratification.