# Exploring novel strategies for immunoprevention of estrogen receptor negative breast cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $450,168

## Abstract

Summary
In 2020, breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in women.
Compared to estrogen receptor (ER)-positive breast cancers, ER-negative (ER-) breast cancers have worse
prognoses and no effective prevention strategies. In this study, we will explore new strategies for
immunoprevention of ER- breast cancer. Inducing potent anti-tumor immunity for prevention of poorly
immunogenic breast cancers has been highly challenging. Engagement and expansion of activated dendritic
cells (DCs) could facilitate broad and efficient anti-tumor immunities. However, certain existing DC stimulators
(e.g., agonists of toll-like receptors and STING) also triggered adverse immune responses. For cancer
prevention, it is imperative to develop safe and effective approaches to boost DC immunity. To this end, we
screened for dietary supplements that increase DC activities and identified natural vitamin E (VitE) as a stimulator
of DC functions. Excitingly, we found that breast cancer patients who took VitE during immunotherapies had a
significantly better survival rate and improved therapeutic response than patients who didn’t take VitE,
suggesting that VitE administration may potentiate anti-tumor immunity. Indeed, systemic (oral) administration
and local (at injection site together with cancer vaccines) delivery of VitE significantly prolonged tumor-free
survival in ER- mammary tumor mouse models that didn’t respond to cancer vaccines alone. These data led us
to hypothesize that VitE administration, via reinforcing DC activation and antigen presentation, enhances
immunoprevention of ER- breast cancer by cancer vaccines. We will test whether VitE could enhance cancer
vaccine-induced immune surveillance and prevent/delay tumor initiation/progression in genetic engineered
mouse models of (HER2+ and basal-like subtypes) ER- mammary tumors and the CD34+ humanized mouse
models (for prevention of human ER- breast cancers) (Aim1). As a proof of concept, we will primarily use a triple-
antigen (tumor associated antigens neu/IGFBP-2/IGF-IR) peptide vaccine (TAVac) for proposed studies since
TAVac has shown partial efficacy in delaying tumor progression in ER- mammary tumor mouse models.
Importantly, corresponding DNA vaccines against human HER2/IGFBP-2/IGF-IR are currently under phase I/II
clinical studies for prevention of HER2+ and HER2- breast cancer recurrence. To gain mechanistic insights into
how VitE potentiates anti-tumor immunity, we will investigate i) the global effect of VitE on the immune cell
landscape by mass cytometry (CyTOF); ii) the impact of VitE on DC and T-cell subset compositions, functionality
and signaling networks; iii) major immunophenotype changes critical for VitE-enhanced immunoprevention; iv)
how VitE prompts antigen processing/presentation in DCs and whether VitE functions through SHP1, a critical
DC checkpoint (Aim2). Finally, we will test novel strategies to further improve the immunoprevention efficacy
against...

## Key facts

- **NIH application ID:** 10757443
- **Project number:** 5R01CA270010-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Dihua Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $450,168
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757443

## Citation

> US National Institutes of Health, RePORTER application 10757443, Exploring novel strategies for immunoprevention of estrogen receptor negative breast cancer (5R01CA270010-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10757443. Licensed CC0.

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