# Targeting Neoantigens in Triple Negative Breast Cancer

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $637,836

## Abstract

PROJECT SUMMARY/ABSTRACT
Neoantigens have been identified by us and others as important targets of immunotherapy in the context of
checkpoint blockade therapy, adoptive cell therapy, and vaccine therapy. We have recently initiated two phase
1 clinical trials of first generation neoantigen vaccines in breast cancer based on the neoantigen DNA vaccine
and synthetic long peptide vaccine platforms. In preclinical models, we have optimized sequencing and epitope
prediction algorithms for the identification and prioritization of neoantigens, and we have leveraged innovative
technologies (CyTOF, single cell RNA sequencing) to comprehensively interrogate the immune response to
neoantigen vaccination and other cancer immunotherapies. We propose to build on these observations by
performing a randomized phase 1 trial of neoantigen DNA vaccine alone vs. neoantigen DNA vaccine plus
anti-PD-L1, in patients with persistent triple negative breast cancer (TNBC) following neoadjuvant
chemotherapy. The overall hypothesis is that enhancing neoantigen-specific T cell responses can improve
clinical outcomes in TNBC. This hypothesis will be tested by completing the following aims:
Specific Aim 1. Test the hypothesis that neoantigen vaccines +/- anti-PD-L1 can induce and/or enhance
neoantigen-specific T cell responses. We have recently initiated a randomized phase 1 clinical trial of
neoantigen DNA vaccines +/- anti-PD-L1 in TNBC patients with persistent disease following neoadjuvant
chemotherapy. Next-generation sequencing and epitope prediction algorithms will be used to prioritize
neoantigens. Neoantigen DNA vaccines will be designed and manufactured in the GMP facility at SCC.
Specific Aim 2: Test the hypothesis that targeting tumor-associated macrophages (TAM) can enhance
neoantigen-specific T cell responses in TNBC. Both embryonically-derived tissue-resident TAM and
inflammatory monocyte-derived TAM restrain antitumor immunity in TNBC. We propose to combine
CSF1/CSF1R blockade with CCR2 inhibition to simultaneously target both sources of TAM in the context of
neoantigen vaccination in two mouse breast cancer models. The tumor microenvironment will be characterized
by CyTOF and single cell RNA sequencing.
Specific Aim 3: Test the hypothesis that a neoantigen simian Ad vector vaccine "prime" followed by a
neoantigen DNA vaccine "boost" can enhance the response to breast cancer neoantigens. We propose
a "prime/boost" strategy consisting of a simian recombinant Ad vaccine "prime," followed by a plasmid DNA
vaccine "boost." This "prime/boost" neoantigen vaccine strategy represents a state-of-the-art vaccine strategy
to more effectively induce antitumor immunity, and leverages expertise at WUSM within the fields of
neoantigen DNA vaccines and recombinant Ad vector vaccines. Photocleavable tetramer analysis, CyTOF,
and single cell RNA sequencing will be performed on neoantigen-specific T cells in the peripheral blood and
the tumor microenvironment to rigorously evaluate ...

## Key facts

- **NIH application ID:** 9980320
- **Project number:** 5R01CA240983-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** William E. Gillanders
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $637,836
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980320

## Citation

> US National Institutes of Health, RePORTER application 9980320, Targeting Neoantigens in Triple Negative Breast Cancer (5R01CA240983-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980320. Licensed CC0.

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