# Laser Interstitial Thermal Therapy for the Treatment of Glioblastoma

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2021 · $440,000

## Abstract

Project Summary
Very limited options are available for treating glioblastoma, the most common primary brain tumor in humans.
Effective surgical options are particularly lacking, although resection has been shown to consistently be of value
for some patients with glioma. Laser interstitial thermal therapy (LITT) is in clinical use for treating primary brain
tumors, but how this technology affects the tumor microenvironment is poorly understood. We have generated
an immunocompetent RCAS/Ntv-a murine model of LITT with survivable brain lesions that can be used to
characterize LITT-induced changes in the tumor microenvironment. Importantly, we have extensive experience
studying the tumor microenvironment in the context of endogenously forming, high-grade gliomas in this mouse
model. We hypothesize that LITT-induced thermal damage can create a tumor microenvironment more
responsive to adjunct therapies. In Specific Aim 1, we will characterize the longitudinal effects of LITT on the
tumor microenvironment by examining treated mice for an influx of immune cells and induced genetic changes
using NanoString technology. We will also use a murine anti-PD-1 antibody, which we have recently shown to
be effective against glioblastoma in our tumor model, in neoadjuvant and adjuvant settings to determine if its
efficacy can be enhanced by LITT. While anti-PD-1 monotherapy for glioblastoma has not been efficacious due
to the low immunogenicity of the tumor environment, its use in the context of LITT-induced immune cell infiltration
and neoantigen formation may lead to greater therapeutic benefits against this type of cancer. In Specific Aim 2,
we will determine the ability of thermally-released doxorubicin from nanoparticles to improve survival rates of
tumor-bearing mice following LITT. Although in clinical trials for extracranial cancers, the use of heat-activated
nanoparticles for treating brain tumors is quite novel. Systemic doxorubicin has shown some benefit in other
murine models of brain cancer, but its heat-activated nanoparticle release may permit more localized delivery
and extended treatment beyond the LITT penumbra to the infiltrating edge of the tumor, which is the most
common source of glioblastoma recurrence. With the completion of these aims, we will better understand how
the population immune cells in the tumor microenvironment changes in response to thermal therapy. We will
also understand what genetic programs are upregulated in the tumor microenvironment after thermal therapy
potentially giving us new therapeutic targets to combine with LITT. The overall goal of this proposal is to
demonstrate how thermal ablation affects the tumor microenvironment and how it can be combined with other
treatments to improve outcomes for patients with glioblastoma. Given the availability of the treatments being
investigated there is a low threshold for the clinical application of our results. These studies will serve as the
groundwork for more extensive studie...

## Key facts

- **NIH application ID:** 10285714
- **Project number:** 1R21NS123589-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ganesh Rao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285714

## Citation

> US National Institutes of Health, RePORTER application 10285714, Laser Interstitial Thermal Therapy for the Treatment of Glioblastoma (1R21NS123589-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10285714. Licensed CC0.

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