# Combinatorial Strategies for the Treatment of Brain Metastases

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $181,156

## Abstract

Project Summary/Abstract
The incidence of brain metastasis from primary breast cancer is steadily increasing with approximately 15% of
patients being diagnosed with brain metastasis. This is particularly grim for patients with Triple Negative Breast
Cancer whose incidence can reach up to 35% during their lifetime. Progression of disease is associated with
many factors including loss of anti-tumor immunosurveillance, which allows growth and metastatic cancer cells.
Recent clinical trials examining the potential benefits of immunotherapeutics in these populations have shown
limited responses. Therefore, we must develop novel therapeutic strategies to re-store immune cytotoxic cells
actions to treat metastasis of breast cancer to reduce disease morbidity and mortality. We have recently
published that the receptor CD47 is over expressed in invasive breast cancer. CD47 is a widely expressed
receptor essential for the regulation of innate and adaptive immune responses. We recently discovered that
blockade of CD47 increases CD8+ T cell infiltration and increases T cell mediated cancer cell cytotoxicity,
indicating that targeting CD47 may serve as an immunotherapy to reduce tumor burden. Furthermore, we have
shown that these receptors regulates metabolism as a response to stress such as ionizing radiation. This effect
on metabolism could also be responsible for allowing T cells to upregulate their metabolism to meet their
biosynthetic needs in the harsh conditions of the tumor microenvironment. This would enhance T cell effector
function allowing specific cytotoxicity of cancer cells. Our published data shows that blockade of CD47
enhances radiation growth delay in several preclinical models. Our recently published evidence shows that
blockade of CD47 reduces metastasis formation in the 4T1 murine breast cancer model. Together this data
supports our hypothesis that anti-CD47 immunotherapy could be a treatment for metastatic brain cancer. We
propose to study this paradigm with the following specific aims: 1) Determine whether CD47 blockade plus
whole brain irradiation inhibits established breast cancer brain metastasis. 2) Determine whether anti-CD47
immunotherapy potentiates abscopal effects of radiotherapy to inhibit metastasis.

## Key facts

- **NIH application ID:** 10111492
- **Project number:** 5R21CA249349-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** David R. Soto Pantoja
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $181,156
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111492

## Citation

> US National Institutes of Health, RePORTER application 10111492, Combinatorial Strategies for the Treatment of Brain Metastases (5R21CA249349-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10111492. Licensed CC0.

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