# Targeting Neoantigens in Glioblastoma

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $463,723

## Abstract

PROJECT SUMMARY
This proposal focuses on targeting neoantigens in malignant brain tumors in well defined orthotopic, syngeneic
preclinical models, understanding how type 1 conventional dendritic cells (cDC1) prime neoantigens, and how
immune responses to neoantigens develop in newly diagnosed glioblastoma (GBM) patients enrolled in a
novel clinical trial combining personalized vaccination with checkpoint blockade. GBM remains a lethal cancer
and carries a median survival of 15 months with standard-of-care treatments, highlighting a clear need for
more effective treatments. The application of genomics to immunotherapeutic approaches is an exciting area
of investigation in many cancer types, and this proposal employs this methodology. This nexus, termed “cancer
immunogenomics”, is used to identify tumor-specific somatic mutations that may be processed and presented
on major histocompatibility molecules. These “neoantigens” can be recognized by the immune system and
form the basis for anti-tumor immune responses. We have applied the cancer immunogenomics approach to
the study of GBM both in preclinical models as well as in a novel personalized immuno-oncology cancer
vaccine program for GBM patients. However, in order to fully exploit the potential of targeting neoantigens in
GBM, further work is needed to understand whether targeting multiple neoantigen targets using polyvalent
vaccines can improve tumor control and how neoantigens are presented to the immune system in brain
cancers. How antigen is presented in the central nervous system remains unclear, and understanding the
immunobiology of this process is inextricably linked to effective neoantigen targeting. In parallel, it is critical to
determine how anti-tumor immunity is amplified in patients treated with personalized cancer vaccines in
combination with immunopotentiating checkpoint blockade therapies. To this end, we are applying cancer
immunogenomics preclinically and translationally to address these key questions. In Aim 1, we will determine
the effectiveness of polyvlalent neoantigen vaccination targeting MHC class and and/or MHC class II
neoantigens on survival and the immunologic effects of these vaccines on the brain tumor microenvironment.
In Aim 2, we will test the hypothesis that cDC1 present neoantigen in vivo and can augment the efficacy of
neoantigen-targeting vaccines. We will also further characterize the anatomic location of this critical cell
population during the anti-tumor immune response. In Aim 3, we will perform correlative analysis of a novel
clinical trial we are conducting to determine whether checkpoint blockade agents augment the immune
responses generated with personalized vaccines and whether the genomes of recurrent tumors that progress
on this trial are remodeled and/or show evidence of neoantigen specific cancer immunoediting. Together,
these Aims will provide new insights into an immunogenomics-centered approach to treating GBM as well as
the immunobiology of...

## Key facts

- **NIH application ID:** 10240743
- **Project number:** 5R01NS112712-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gavin Peter Dunn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $463,723
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-10-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240743

## Citation

> US National Institutes of Health, RePORTER application 10240743, Targeting Neoantigens in Glioblastoma (5R01NS112712-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240743. Licensed CC0.

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