# Clinically Actionable Neoantigens in Non-Small Cell Lung Cancer

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2020 · —

## Abstract

Clinically actionable neoantigens in non-small cell lung cancer
Lung cancer is the leading cause of cancer death among US Veterans as well as the world's leading cause of
cancer death. Environmental exposure and tobacco use among Veterans operate together to increase risk.
Unleashing the immune response against pulmonary premalignancy could transform therapy and outcomes.
Here, we propose to lay the ground work for lung “cancer interception,” a strategy that seeks to block the
progression of premalignancy to invasive cancer. In our preliminary studies we have begun to evaluate the
mutational landscape of pulmonary premalignancy and the associated premalignant microenvironment by whole
exome DNA sequencing and immunohistochemistry. Remarkably, we find frequent immune-effector cell
infiltration as well as evidence of immune suppression in pulmonary premalignancy. These findings lead us to
hypothesize that premalignant-associated neoantigens (PANs) are recognized and elicit immune responses at
the earliest points of lung adenocarcinoma development. This research will identify neoepitopes that can be
targeted before the development of invasive lung cancer, thus shifting the approach to disease interception
through immunoprevention and treatment of the very earliest phase of the disease.
The specific aims are: 1) To utilize whole exome DNA sequencing (WES) to determine computationally-defined
neoantigens in matched sets of primary tumor, premalignant lesions and adjacent histologically normal lung
tissues. 2) To identify functionally relevant neoepitopes associated with tumor progression: Two sources of T
cells, one from TIL, the other from peripheral blood PD1+ T cells, will be used to identify neoepitope-specific
CD8+ T cells. To improve screening efficiency, we will focus on neoantigens shared between pre-malignant
lesions and primary tumors that are potentially progression-relevant. Functional assays will be performed to
verify the identified neoepitopes. This will lead to patient-tailored neoepitopes for future vaccine or adoptive cell
therapies for non-small cell lung cancer (NSCLC). 3) To relate the immune contexture to WES-defined mutational
landscapes in premalignancy and the associated tumor we will: 3A) Perform quantitative multiplexed
immunofluorescent staining of the same specimens utilized in the first two aims to assess the regulators of cell-
mediated immunity and to relate this to the mutational landscapes and neoepitopes of the premalignant lesions
and tumors, 3B) Evaluate gene expression utilizing a Nanostring panel of 770 immune-related genes and, 3C)
Integrate findings from WES, gene expression and tissue immunostaining to define the landscape of
adenocarcinoma pulmonary premalignancy. This research seeks to transform the approach to both the
prevention and treatment of lung adenocarcinoma by discovery of functional neoepitopes that can be utilized in
the development of vaccines and adoptive therapies to intercept disease at the e...

## Key facts

- **NIH application ID:** 9814093
- **Project number:** 5I01CX000345-08
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Steven M. Dubinett
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-04-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9814093

## Citation

> US National Institutes of Health, RePORTER application 9814093, Clinically Actionable Neoantigens in Non-Small Cell Lung Cancer (5I01CX000345-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9814093. Licensed CC0.

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