# IL-1-based immunotherapy in HNSCC

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2022 · —

## Abstract

Immunotherapy-based strategies (i.e. anti-programmed cell death protein-1 (anti-PD1) are highly suitable
options for VA patients given the more favorable toxicity profile compared to chemotherapy strategies and the
remarkable durable tumor responses that can be triggered. However, only a minority of patients derive benefit
from single-agent immunotherapies and improvements are needed before routine use of anti-PD1 agents as
first-line treatment. Therefore there remains a significant need to identify novel alternative immunotherapeutic
strategies in order to improve survival outcomes for VA HNSCC patients. We propose that interleukin-1 (IL-1)
ligands (e.g. IL-1α and/or IL-1β) may represent an effective immunotherapy in HNSCC patients. IL-1 signaling
can activate a robust anti-tumor immune response via increased antigen presentation by dendritic cells (DCs),
triggering of natural killer (NK) cell activity, and activation/proliferation of CD4+ and cytotoxic CD8+ T cells.
This suggests that increasing levels of circulating IL-1 ligands may trigger anti-tumor immunity and enhance
HNSCC tumor response to other therapeutic strategies that can induce anti-tumor responses such as
radiotherapy and anti-PD1 therapy. Our preliminary data has shown unprecedented and durable T cell-
dependent anti-tumor responses with a single intraperitoneal administration of an IL-1α polyanhydride
nanoparticle (IL-1αNP) formulation to mice as a single agent. Additionally, in comparison to administration of
recombinant IL-1α which elicited severe weight loss and toxicity, IL-1αNPs showed no obvious signs of toxicity.
Based on this data we believe that IL-1α administration using nanoparticle delivery may represent a promising
immunotherapeutic approach AND adjuvant to other agents approved for the treatment of HNSCC that trigger
anti-tumor immune responses (e.g. radiotherapy and anti-PD1). We hypothesize that IL-1NPs will trigger an
anti-tumor immune response and enhance HNSCC tumor response to radiotherapy and anti-PD1 therapy. Aim
1 will evaluate the therapeutic efficacy and safety profile of IL-1NPs; Aim 2 will examine if IL-1NPs will enhance
HNSCC tumor response to radiotherapy; and Aim 3 will examine if IL-1NPs will enhance HNSCC tumor
response to anti-PD1 immunotherapy. If successful, IL-1NP delivery would represent a promising
immunotherapeutic approach for VA HNSCC patients and we are hopeful that this work will lead to the clinical
evaluation of novel combination immunotherapy strategies that include IL-1NP delivery.

## Key facts

- **NIH application ID:** 10438533
- **Project number:** 5I01BX004829-03
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Andrean Llewela Burnett
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438533

## Citation

> US National Institutes of Health, RePORTER application 10438533, IL-1-based immunotherapy in HNSCC (5I01BX004829-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438533. Licensed CC0.

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