# Generating a Systemic Immune Response Using Localized Delivery of Chemotherapy in Brain Tumors

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $359,550

## Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is associated with a
dismal prognosis. Immunotherapy has demonstrated potential to generate durable antitumor activity in other
types of cancer. In particular, agents that selectively target checkpoint molecules, such as anti-CTLA-4 and
anti-PD-1 antibodies, have accelerated the field of cancer immunotherapy by directly combating the tumor's
mechanisms of immune evasion. Notable results with these agents have already been reported in advanced
melanoma, renal cell carcinoma, and lung cancer and trials are underway in GBM. Chemotherapy, which is
part of the standard of care for patients with GBM, has been associated with immunosuppressive effects and
with myeloablative results. Recent data from our laboratory shows that local chemotherapy may be a better
alternative to systemic chemotherapy given that it avoids these untoward effects. The main goal of this
proposal is to understand the main mechanisms by which GBM evades the immune system and how to thwart
these mechanisms with local chemotherapy and checkpoint blockade to enhance an effective immune
response against GBM. Our data demonstrates that local chemotherapy in combination with anti-PD-1
increases survival and provides an increase in memory T cells in an orthotopic glioma model and protects
against tumor re-challenge. We propose to study: 1. Potential biomarkers of response in patients with GBM
treated with LC and anti-PD-1 therapy as part of an ongoing clinical trial at our institution. 2. The neoantigen
profile generated by LC in intracranial chemosensitive and chemoresistant murine gliomas, to determine the
impact on TCR diversity and anti-tumor immune response. 3. The location and identity of APCs responsible for
antigen presentation induced by LC. These data will have direct clinical relevance for the findings and can be
translational into clinical trials and patient care. We expect that the data generated from these studies will
provide novel insights into a previously unexplored aspect of chemotherapy and serve as a foundation for
optimizing the efficacy of therapy and host immune function against GBM. The knowledge obtained from this
study will undoubtedly result in better therapeutic alternatives for current unsuccessful treatment for patients
with GBM.

## Key facts

- **NIH application ID:** 10177959
- **Project number:** 5R01CA230285-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $359,550
- **Award type:** 5
- **Project period:** 2019-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177959

## Citation

> US National Institutes of Health, RePORTER application 10177959, Generating a Systemic Immune Response Using Localized Delivery of Chemotherapy in Brain Tumors (5R01CA230285-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177959. Licensed CC0.

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