# Elucidating resistance mechanisms and enhancing response to immune checkpoint blockade in central nervous system metastases from breast cancer

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $701,408

## Abstract

PROJECT SUMMARY
Metastases to the central nervous system (CNS) are a common complication of breast cancer. Prognosis is
typically on the order of a few months. Immunotherapies have revolutionized the management of many types of
cancers. However, these agents have not been systematically studied in the management of CNS metastases
from breast cancer. We are conducting several Phase II trials to explore the role of newly developed
immunotherapies in CNS metastases. Three of our trials have already met primary endpoint, with a subset of
patients with breast cancer showing responses to immunotherapy. We propose to study cancer genetic and
immune phenotypic changes in samples collected from patients before, during and after immunotherapy. Our
overarching objective is to characterize mechanisms of resistance to immunotherapy in CNS metastases. To
achieve this, we will chart the co-evolution of cancer and the immune system over time and anatomical location
during immunotherapy by profiling DNA and RNA from cancer tissues, peripheral blood, and cerebrospinal fluid
(CSF). Notably, using cutting edge single-cell technologies, we will examine alterations to the cancer genome
and immune cell behaviors at unprecedented resolution. Furthermore, in our innovative mouse models of brain
metastases, we will study novel combination therapies, including CDK inhibition with immune-checkpoint
blockade, to augment the efficacy of immunotherapy. We believe that this work has the potential to uncover basic
mechanisms of treatment-failure in these patients and that these discoveries will have tremendous translational
potential as a basis on which to refine existing immunotherapy protocols and develop novel treatment strategies.

## Key facts

- **NIH application ID:** 10997794
- **Project number:** 1R01CA294793-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Priscilla Kaliopi Brastianos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $701,408
- **Award type:** 1
- **Project period:** 2024-07-12 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997794

## Citation

> US National Institutes of Health, RePORTER application 10997794, Elucidating resistance mechanisms and enhancing response to immune checkpoint blockade in central nervous system metastases from breast cancer (1R01CA294793-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997794. Licensed CC0.

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