# An Engineered Nanocarrier Platform for Enhancing Immune Responses to Neoantigen-Targeted Cancer Vaccines

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $46,036

## Abstract

Project Summary
Vaccines targeting cancer neoantigens have the potential to enhance the magnitude, function, and duration of
an anti-tumor T cell response, offering a promising strategy to improve response rates to immune checkpoint
blockade (ICB). However, neoantigenic peptides are typically poorly immunogenic and even when administered
in combination with an adjuvant do not elicit a sufficiently strong anti-tumor T cell response for maximal efficacy.
This can be attributed to several factors, including poor lymphatic accumulation, low cellular uptake by antigen
presenting cells (APCs), and inefficient cross-presentation to CD8+ T cells. The goal of this research is to design
and evaluate a nanoparticle vaccine platform to potentiate cellular immunity against peptide neoantigens. We
will do this through the design of nanoparticle vaccine technology that overcomes these drug delivery challenges
through several, intertwined, methods: 1) Particles will be designed to allow simultaneous delivery of antigen
and adjuvant to the same APC, resulting in coordinated expression of co-stimulatory markers and presentation
of antigen, which will enhance downstream T cell activation. 2) Nanoparticles will be engineered with pH-
responsive properties that promote cytosolic delivery of the antigen to increase cross presentation on MHC class
I molecules, resulting in a stronger CD8+ T cell response. 3) A rapid and facile strategy for loading of peptide
antigens will be employed, which will allow patient-specific neoantigenic peptides of diverse chemical properties
to be efficiently integrated into the nanoparticle vaccine. 4) Nanoparticle properties will be optimized to allow for
delivery of multiple, synergistically-acting adjuvants in order to further enhance T cell responses. We propose to
accomplish this through two Specific Aims: 1) We will develop a nanotechnology for co-delivery of STING
agonists and patient-specific peptide neoantigens. Peptide and nanoparticle properties will be optimized, the
ability of the vaccine to activate an antigen-specific immune response will be assessed in vitro and in vivo, and
efficacy will be evaluated using know murine neoantigens. 2) We will investigate adjuvant synergy between
STING and toll-like receptor agonists by evaluating their ability to enhance antigen cross-presentation on APCs
and induce antigen-specific T cell responses. Synergistic combinations will be co-loaded into the nanoparticle
vaccine platform and efficacy will be evaluated in vitro and in vivo. We hypothesize that this new vaccine platform
will generate a strong patient-specific, anti-tumor T cell response targeting a diversity of neoantigens, resulting
in enhanced responses to ICB. This research will contribute to our growing understanding of how materials can
be engineered to modulate immune responses and will result in a versatile new drug delivery technology that
has potential to improve personalized cancer vaccines. This proposal also describes a ...

## Key facts

- **NIH application ID:** 10141981
- **Project number:** 1F31CA257275-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jessalyn J Baljon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-01-13 → 2024-01-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141981

## Citation

> US National Institutes of Health, RePORTER application 10141981, An Engineered Nanocarrier Platform for Enhancing Immune Responses to Neoantigen-Targeted Cancer Vaccines (1F31CA257275-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10141981. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*