# Engineered Vaccines for Neoantigen Targeted Cancer Immunotherapy

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $221,278

## Abstract

PROJECT SUMMARY
Immune checkpoint blockade (ICB) is an immunotherapy that is revolutionizing cancer treatment, but is
effective in a minority of patients. Across many solid tumor types, this can largely be ascribed to an insufficient
number, diversity, and/or function of endogenously generated, pre-existing T cells that recognize tumor
neoantigens and infiltrate tumors. Therefore, there is a critical need for new strategies to bolster the
magnitude, breadth, and quality of neoantigen-specific T cells, to recruit cytotoxic CD8+ T cells to tumors, and
to amplify their expansion, effector function, and persistence. Towards this goal, we propose a new strategy for
neoantigen-targeted cancer immunotherapy. Our approach leverages a STING-activating nanoparticle vaccine
(STAN-V) that we have designed to overcome several critical immunopharmacological barriers that limit cancer
vaccine efficacy. The STAN-V platform is based on polymer nanoparticles engineered to enhance intracellular
co-delivery of peptide neoantigen and agonists of stimulator of interferon genes (STING), a design that we
have demonstrated stimulates potent neoantigen-specific CD8+ T cells and increases response to ICB. Our
objective in this R01 application is to advance and mature STAN-V as a universal platform for neoantigen-
targeted cancer vaccines. We will accomplish this through the following Specific Aims. First, we will develop
and optimize a facile strategy for rapid fabrication of STAN-Vs based on spontaneous and efficient loading of
neoantigenic peptides designed with optimized lipophilic domains. We will evaluate the capacity of this
approach to increase the magnitude and breadth of neoantigen-specific T cell responses to physicochemically
diverse neoantigens. As such, we expect these studies to advance the translational-readiness of STAN-Vs as
a personalized vaccine technology. Second, we will leverage the unique morphology and properties of STAN-
Vs to develop and optimize a novel adjuvant combination based on coordinated co-packaging and co-delivery
of STING and TLR agonists. We will systematically explore the effect of combinatorial adjuvant delivery on
innate and adaptive immunity, studies that we expect will yield an optimized adjuvant combination for
stimulating antitumor cellular immunity. Third, we will devise and test a new approach for enhancing tumor
homing and infiltration of T cells elicited via vaccination. This strategy will leverage systemic administration of a
nanoparticle STING agonist that reshapes the tumor milieu to enhance T cell infiltration, proliferation, and
function. Overall, these studies will advance STAN-Vs as an enabling and versatile technology for stimulating
robust neoantigen-specific T cell responses and improving outcomes of immunotherapy across many cancers.

## Key facts

- **NIH application ID:** 10894059
- **Project number:** 5R01CA266767-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** John Tanner Wilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $221,278
- **Award type:** 5
- **Project period:** 2022-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894059

## Citation

> US National Institutes of Health, RePORTER application 10894059, Engineered Vaccines for Neoantigen Targeted Cancer Immunotherapy (5R01CA266767-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894059. Licensed CC0.

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