# Defining neoantigen immunodominance for antigen selection and biomarker discovery in human pancreatic cancer immunotherapy

> **NIH NIH U01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $615,450

## Abstract

PROJECT SUMMARY
Checkpoint blockade immunotherapy has induced dramatic responses in treatment refractory cancers by
targeting neoantigens encoded by cancer-specific mutations. Neoantigen load predicts immunotherapeutic
response, validating antigen identification as a rational strategy of biomarker discovery. Pancreatic
adenocarcinoma (PDAC) however has shown limited efficacy to checkpoint blockade immunotherapy due to
presumed neoantigen paucity. However, systematic antigen discovery in PDAC is lacking.
3% of PDAC patients survive > 5 years (long term survivors). As T cell immunity may explain this extreme
outcome, they represent the ideal cohort for deep antigen discovery. Using genomic, molecular, and cellular
immunoprofiling, computational evolutionary modeling, and neoantigen discovery in these rare long term
survivors (n=82), we have discovered that neoantigen quality, but not quantity, is prognostic of survival, and
that long term survivors evidence lasting neoantigen-specific T cell immunity. The scientific objectives of this
proposal are to address questions essential to translate these findings - 1) is there stage and treatment-
specific neoantigen heterogeneity, 2) can neoantigens be identified in the peripheral blood, and 3) can
neoantigen quality predict response to immunotherapy. The translational objective is to develop novel tissue
and blood-based biomarkers for rational patient and target selection for immunotherapy.
The proposal utilizes several highly unique tissue collection strategies – a) laparoscopic multi-site biopsies to
identify stage-specific heterogeneity, b) serial pre- and post-chemotherapy assessment for treatment-specific
modulation, and c) evaluation of neoantigen quality as a predictive biomarker on a large, immunotherapeutic
PDAC trial. This initiative will also for the first time develop the ability to identify neoantigens in circulating
exosomes for blood-based biomarker assessment. The research methodology employs next generation
sequencing, transcriptional profiling, computational biophysical modeling, clonotypic T cell profiling, neoantigen
discovery, and functional assessments to evaluate the prognostic, predictive, and therapeutic potential of
neoantigens. The team comprises of world-class expert junior and senior investigators in a broad range of
highly relevant disciplines from Memorial Sloan Kettering Cancer Center, Meyer Cancer Center at the Weill
Cornell Medical Center, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and the Institute
for Advanced Study. This initiative is directly relevant to the primary objective to develop novel biomarkers and
T cell antigenic targets for the successful application of immunotherapy in PDAC.

## Key facts

- **NIH application ID:** 10242452
- **Project number:** 4U01CA224175-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Vinod P Balachandran
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $615,450
- **Award type:** 4N
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242452

## Citation

> US National Institutes of Health, RePORTER application 10242452, Defining neoantigen immunodominance for antigen selection and biomarker discovery in human pancreatic cancer immunotherapy (4U01CA224175-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10242452. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*