# Remodeling host immunity in oral cancer with personalized RNA nanoparticle vaccines

> **NIH NIH K08** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $155,304

## Abstract

PROJECT SUMMARY/ABSTRACT
 Oral cavity squamous cell carcinoma (OCSCC) is a very aggressive and deadly disease with poor survival
rates following maximal treatments such as surgery and chemoradiotherapy. The immunosuppressive tumor
microenvironment (TME) is a major barrier of response to traditional and immune based therapies with only
~15% of patients with recurrent head and neck cancer responding to immune checkpoint inhibitors. Myeloid cells
are; abundant in the TME, key mediators of T cell function, and can influence clinical outcomes both positively
and negatively. We seek to understand the contribution of myeloid cells to the immunosuppressive TME and
advance strategies to modulate these cells in a favorable way, to enhance OCSCC tumor killing.
 Our group has developed a novel vaccine treatment platform that can reprogram the intratumoral and
peripheral myeloid cell compartment to an anti-tumor state. This platform leverages the use of clinically
translatable lipid nanoparticles (NPs), combined with personalized tumor derived mRNA (TDRNA) that
simultaneously functions as both a vaccine and an immunomodulating agent. We have demonstrated that
TDRNA-NP vaccines have significant anti-tumor activity in OCSCC preclinical models and synergize with
immune checkpoint inhibitors. In Aim 1, we will determine the mechanism of TDRNA-NP induced myeloid cell
mediated immune responses by investigating vaccine induced myeloid cell proliferation, activation and
trafficking in preclinical models of OCSCC. In Aim 2, we will identify the mechanistic role of myeloid cells
in the synergy between TDRNA-NP vaccines and immune checkpoint inhibitors in murine models of
OCSCC. In Aim 3, we will examine the safety, efficacy and immunogenicity of TDRNA-NPs in client-owned
felines with spontaneously occurring oral squamous cell carcinoma. These studies will give us insight into
the role of the myeloid cell compartment in OCSCC and advance a promising vaccine technology towards
first-in-human clinical trials. The P.I. of this project is a head and neck surgical oncologist and
witnesses the daily impact head and neck cancer has on patients and recognizes the need to
improve patient care through translational research. She is an active member of the Head and Neck
oncology program, is strongly supported by her department, and has a mentoring team comprised of world
renowned expert tumor immunologist/translational researchers, and head and neck surgeon-scientists. This
mentored training and educational program has been carefully designed with research and career objectives
that will allow the P.I. to progress toward becoming an expert head and neck cancer immunologist and
translational researcher. In summary, this proposal has significant potential to dramatically impact the lives
of patients with OCSCC and will provide substantial training and mentorship for the P.I. to become an
independent investigator.

## Key facts

- **NIH application ID:** 10427461
- **Project number:** 5K08DE029503-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Natalie Lea Silver
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $155,304
- **Award type:** 5
- **Project period:** 2022-01-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427461

## Citation

> US National Institutes of Health, RePORTER application 10427461, Remodeling host immunity in oral cancer with personalized RNA nanoparticle vaccines (5K08DE029503-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427461. Licensed CC0.

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