# Project 1:  Targeting immunotherapy-induced resistance with DC vaccination and PD-1/CSF-1R inhibition

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $378,369

## Abstract

PROJECT SUMMARY/ABSTRACT – Project 1
The lack of effective treatments for glioblastoma (GBM) patients remains a significant health problem and
highlights the need for novel and innovative approaches. Immunotherapy is an appealing strategy because of
the potential ability for immune cells to traffic to and destroy infiltrating tumor cells in the brain. For the past 15
years, our group and others have been testing active vaccination strategies, such as dendritic cells (DC) pulsed
with tumor lysate, to induce antitumor immunity in glioblastoma patients. From the interim results of the clinical
trial we initiated in our current SPORE funding period, we found that in addition to inducing T-cell infiltration into
brain tumors, DC vaccination + anti-PD1 blockade may also create a pro-inflammatory environment within the
tumor that induces the immigration of immunosuppressive myeloid cells (TIM). These cells are phenotypically
similar to the myeloid cells that dominantly attenuate the T-cell response to chronic viral infections, and may
counteract the effective anti-tumor T-cell responses induced by DC vaccination within the tumor
microenvironment. Therapies that target myeloid cells within the tumor microenvironment represent a promising
new strategy. As such, inhibition of these myeloid cells using a CSF-1R inhibitor, in conjunction with autologous
tumor lysate-pulsed DC vaccination (ATL-DC) and PD-1 mAb blockade, resulted in significantly prolonged
survival in tumor-bearing animals with large, well-established intracranial (i.c.) gliomas. Our hypothesis is that
myeloid cells mediate adaptive immune resistance in response to T cell activation induced by
immunotherapy. In this SPORE Project renewal, we have planned a series of novel pre-clinical studies to re-
polarize myeloid cells, to optimize how the timing and sequence of immunotherapy can influence ant-tumor
immunity, and a new clinical trial to test the first-in-human combination of a new brain penetrant CSF-1R inhibitor
(CSF-1Ri; PLX3397, Daiichi-Sankyo) with DC vaccination and PD-1 mAb blockade (Pembrolizumab, Merck) in
patients with newly diagnosed GBM. A better understanding of the biology of these cellular interactions will
provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type
of brain tumor. These studies span the continuum of translational research in brain tumor immunotherapy, and
will likely provided informative new insights for the development of new, rational immune-based strategies for
brain tumor patients.

## Key facts

- **NIH application ID:** 10673749
- **Project number:** 5P50CA211015-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Robert M Prins
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $378,369
- **Award type:** 5
- **Project period:** 2017-08-11 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673749

## Citation

> US National Institutes of Health, RePORTER application 10673749, Project 1:  Targeting immunotherapy-induced resistance with DC vaccination and PD-1/CSF-1R inhibition (5P50CA211015-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10673749. Licensed CC0.

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