# New Engineering Strategy for Harnessing Immune System against Head and Neck Cancer

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $578,297

## Abstract

Project Summary
Head and neck squamous cell carcinoma (HNSCC) is an extremely aggressive disease with poor overall survival.
Despite the success of immune checkpoint blockade (ICB), current forms of immunotherapy benefit less than
15% of HNSCC patients. Therefore, there exists a critical need for new strategies for achieving powerful and
durable immune responses with minimal toxicity. Our objective in this application is to design and develop new
technological tools for inducing and potentiating T-cell responses against HPV+ HNSCC. To this end, we have
engineered a nanoparticle vaccine delivery vehicle that can efficiently deliver antigens and adjuvant molecules
to antigen-presenting cells and achieve strong T-cell responses with robust cytotoxic potential. In addition, we
have identified a novel strategy for harnessing the immune system by altering the gut microbiome to further
amplify nanovaccine-primed T-cell responses. Here, we seek to conduct structure-function studies to understand
how these biomaterials interface with our immune system and apply the knowledge gained from these basic
studies to potentiate T-cell responses against HPV+ HNSCC. In particular, we will address the following
questions by applying the principles of drug delivery, bioengineering, and vaccinology. Can we utilize our strategy
to promote antigen and adjuvant delivery to antigen-presenting cells, and improve systemic and local T-cell
responses in vivo? Can we employ our vaccine delivery technology to unleash the full cytotoxic potential of T-
cells and reverse immunosuppression within HNSCC? Can we alter the gut microbiome to boost efficacy of
combination immunotherapy? Can we demonstrate their efficacy in orthotopic models of HPV+ HNSCC,
including genetically engineered mouse model of HNSCC? These studies may lead to a novel strategy for
harnessing our immune system as the potential treatment of HPV+ HNSCC. The proposal is fully responsive to
PAR-19-172 as it will: (1) drive the maturation of an innovative technology for precise immune modulation, (2)
create technologies for versatile adjuvant delivery, and (3) enhance the immunotherapeutics for an NIDCR
priority disease.

## Key facts

- **NIH application ID:** 10434134
- **Project number:** 5R01DE030691-02
- **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:** 2022
- **Award amount:** $578,297
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434134

## Citation

> US National Institutes of Health, RePORTER application 10434134, New Engineering Strategy for Harnessing Immune System against Head and Neck Cancer (5R01DE030691-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10434134. Licensed CC0.

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