# Develop a Therapeutic Nano-vaccine against Head and Neck Cancer

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $370,500

## Abstract

PROJECT SUMMARY
 Clinical success of immune checkpoint receptor (ICR) blockade stems from its efficacy in restoring the
effector function of exhausted tumor-infiltrating lymphocytes. But an exclusive effector immune cell-targeted
treatment is prone to failure in hypoimmunogenic cold tumors, which are featured by insufficient elicitation of
tumor-specific T-cell immunity and resistance to immunogenic cytotoxicity. Indeed, about 80% of Oral, Head &
Neck Squamous Cell Carcinoma (HNC) patients do not respond to ICR blockade. Conventional
chemoradiotherapy and surgical management are associated with high morbidity, such as swallowing
problems, dry mouth, fungal infection, dead bone of the jaw, disfigurement, and “lock-jaw”. Deescalating
treatment results in disease progression. Thus, it is urgent to characterize the mechanisms underpinning HNC
hypoimmunogenicity. Our preliminary study identifies type I interferon signaling in the tumor microenvironment
as a key pathway modulating the plasticity of anti-tumor immune response. Type I interferon target genes
promote antigen-presenting cell (APC) and effector cell trafficking to the tumor bed, and enhance APC cross-
priming efficiency. To mitigate the negative impact of cold HNC upon immune activation, we engineered a
nano-vaccine system that potently enhances type I interferon signaling and antigen delivery. Our prototype
nano-vaccine leads to an over 12-fold expansion of tumor-specific T cells in the tumor microenvironment, and
significantly reduces tumor burden. Informed by our results and in response to the FOA, the overarching
hypothesis of the project is: type I interferon signaling is essential to maintain HNC immunogenicity, and our
nano-vaccine sensitizes cold HNC to ICR blockade. To test this hypothesis, three aims are put in place: **(1)
we will characterize the role of type I interferon signaling in modulating HNC immunogenicity; **(2) we will
determine the mechanisms HNC cells employ to dampen type I interferon signaling and promote resistance to
checkpoint blockade; **(3) we will optimize a type I interferon-inducing tumor-specific nano-vaccine system to
break HNC immune tolerance. These goals are in precise alignment with the FOA. (1) We will elucidate the
role of type I interferon signaling in modulating the plasticity of anti-tumor immunity. (2) We will develop a safe,
biocompatible, highly immunogenic and effective nano-vaccine technology to precisely and predictably enrich
tumor antigen-specific T-cell repertoire.

## Key facts

- **NIH application ID:** 9895433
- **Project number:** 5R01DE026728-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yu Leo Lei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,500
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895433

## Citation

> US National Institutes of Health, RePORTER application 9895433, Develop a Therapeutic Nano-vaccine against Head and Neck Cancer (5R01DE026728-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895433. Licensed CC0.

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