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Overview
We develop pipelines for neoantigen discovery and biologic modalities that target tumor-specific epitopes, with the aim of directing the immune system against cancer-defining mutations.
Explore the published evidence
Pembrolizumab and Olaparib in HRD Metastatic Pancreatic Cancer: The POLAR Trial
Phase 2 POLAR trial evaluating maintenance pembrolizumab + olaparib in biomarker-stratified metastatic PDAC. In cohort A (BRCA1/2, PALB2; n=33), median PFS was 8.3 months, median OS 28 months, and 3-year OS 44%; the prespecified primary efficacy threshold was not met. ctDNA dynamics, tumor-infiltrating lymphocytes, and frameshift-indel neoantigens were associated with durable clinical benefit.
- mOS 28 mo
- 3yr OS 44%
- Primary threshold not met
Overview
We develop pipelines for neoantigen discovery and biologic modalities that target tumor-specific epitopes, with the aim of directing the immune system against cancer-defining mutations.
Discovery pipeline
Tumor and germline sequencing define the somatic mutation landscape, from which candidate neoepitopes are predicted and ranked by expression, clonality, and predicted MHC binding.
Frameshift indels and structural events — enriched in HRD tumors — are prioritized because they generate long, tumor-specific peptide stretches that are attractive vaccine and biologic targets.
Selected epitopes are formulated into personalized modalities and tracked immunologically to confirm that the intended T-cell responses are actually induced.
Key findings
Our translational analyses from the POLAR trial showed that frameshift indel neoantigens are associated with durable clinical benefit in HRD tumors — connecting mutational signatures to immune responsiveness.
In collaboration with MSK colleagues, personalized RNA neoantigen vaccines have been shown to stimulate and prime long-lived CD8+ T cells in pancreatic cancer.
Open questions
What distinguishes a neoantigen that drives durable rejection from one that is ignored, and can those features be predicted before treatment?
How should vaccines and biologics be sequenced with DDR-directed and RAS-directed therapy to maximize and sustain anti-tumor immunity?