# Project 1  Extracellular Vesicles (EVs) Role in GBM Pathobiology

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $284,348

## Abstract

Glioblastomas (GBMs) are one of the most difficult cancers to treat. Their success in defying therapy relies in 
large part on their dynamic cellular heterogeneity and on their ability to subvert their environment, in particular 
to create an immune suppressive milieu. This project will address the role of the newly discovered 
communication vehicles in cancer, extracellular vesicles (EVs) which can carry RNA and protein as 
informational molecules. Our goal is to evaluate to what extent EVs produced by these tumors contribute to an 
immune suppressive environment through their interaction with tumor-associated macrophages and microglia 
(TAMs), and to what extent EVs produced by different genetic subtypes of gliomas, and the stem-like cells 
within these tumors, underlie to their ability to re-define themselves and escape therapy. In Aim 1 we will 
assess EV-mediated information transfer between glioma tumors and microglia/macrophages in the tumor 
microenvironment and its effect on immune suppression. In Aim 2 we will evaluate the role of EVs in 
modulating GBM stem-like cell (GSC) phenotypes and therapeutic resistance. Studies will use syngeneic 
mouse glioma models as well as human GBM stem-like neurosphere cultures and patient-derived xenograft in 
mouse models developed with Core C. We will generate an array of vectors to label cells with multiple 
luciferases and fluorescent proteins, as well as create capsules to contain tumor cells while allowing release of 
EVs and/or small molecules within the brain. FACS analysis and RNAseq will be used to define the 
transcriptome of different cell populations in the brain. Biofluids from mice, as well as from GBM patients (Core 
B), will be sent to Project 2 for protein analysis. Correlative analysis of mRNA/ protein contents and GBM 
genotypes will be assessed, as well as how EV contents reflect changes in GBM subtype and resistance to 
therapy. Our findings will be integrated with those of Project 3 in the context of preclinical evaluation of Gene- 
Mediated Cytotoxic Immunotherapy (GMIC) combined with immune checkpoint inhibition. Organizational 
oversight of rigor and reproducibility will be provided by Core A. Studies in this project will serve to inform the 
development of the projected clinical trial by elucidating how EVs influence and report on GBM status, and how 
they can be manipulated to improve this type of immunotherapy in the context of the GBM brain tumors.

## Key facts

- **NIH application ID:** 9939470
- **Project number:** 5P01CA069246-23
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** XANDRA OWENS BREAKEFIELD
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $284,348
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939470

## Citation

> US National Institutes of Health, RePORTER application 9939470, Project 1  Extracellular Vesicles (EVs) Role in GBM Pathobiology (5P01CA069246-23). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9939470. Licensed CC0.

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