# Chemoimmunoprevention of EGFR-Driven Non-Small Cell Lung Cancer

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $640,450

## Abstract

PROJECT SUMMARY
Lung cancer is the leading cause of cancer mortality worldwide (1). More than 80% of lung cancers consist of
non-small cell lung cancer (NSCLC) and activating mutations within EGFR occur in ~50% of Asian patients
and ~20% of Western patients with NSCLC (1). Contrary to prevailing notions, EGFR mutations in NSCLC
occur in both males and females and in both nonsmokers and nonsmokers (1). Thus, targeting EGFR against
development of NSCLC will have significant impact to control this disease. In order to maximize efficacy of
preventive approaches in NSCLC, the initial focus will be directed toward patients with premalignant lesions or
those with previously treated lung cancer. Two promising therapeutic approaches in preventing development of
NSCLC are with interventions designed to attenuate tumor development (chemoprevention) or modulate
immune recognition of tumor (immunoprevention). This multi-PI proposal will test innovative
chemoimmunopreventive strategies for lung cancer, combining the expertise from Dr. You's and Dr. Wang's
research groups in chemoprevention and cancer immunotherapy, respectively. Prior work in Dr. You's
laboratory has established retinoid X receptor (RXR) agonists (bexarotene and an analog UAB30) as potent
chemopreventive agents in mouse models of lung cancer (2, Table 1). Dr. You's group was also the first to
demonstrate remarkable efficacy of an immunopreventive multi-peptide EGFR vaccine against EGFR-driven
lung tumorigenesis (3). Dr. Wang's prior work has established a novel immune checkpoint protein VISTA as a
critical regulator of anti-tumor immunity (4-9), an important contribution given that blockade of immune
checkpoint receptors has been identified as a major breakthrough in cancer treatment (10). Dr. Wang's group
has shown that VISTA-blocking mAb enhances T cell-mediated tumor rejection in multiple preclinical mouse
models (4-9). Given the established efficacy of these aforementioned approaches in controlling tumor growth,
we hypothesize that combinatorial approaches of chemoimmunoprevention will enhance anti-tumor immunity
within the tumor microenvironment (TME), which will inhibit lung tumor progression and recurrence. Three
specific aims are proposed to test this hypothesis. Aim 1 will investigate the immune regulatory role of RXR
agonists in preventing establishment of a tumor microenvironment that suppresses T cell activation against
developing lung cancer. Aim 2 will determine the preventive efficacy of combined treatment of RXR agonists
and a MHCII-restricted EGFR multi-peptide vaccine on EGFR-driven lung tumor progression. Aim 3 will test
the hypothesis that blocking immune checkpoint proteins VISTA and PD-L1 will synergize with RXR
agonists/EGFR vaccine to prevent acquired resistance and tumor recurrence. This proposal is highly
significant because of the potential of chemoimmunoprevention to become a breakthrough preventive
approach for lung cancer.

## Key facts

- **NIH application ID:** 9928030
- **Project number:** 5R01CA223804-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Li Lily Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $640,450
- **Award type:** 5
- **Project period:** 2018-06-07 → 2021-05-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928030

## Citation

> US National Institutes of Health, RePORTER application 9928030, Chemoimmunoprevention of EGFR-Driven Non-Small Cell Lung Cancer (5R01CA223804-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928030. Licensed CC0.

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