IL-1-based immunotherapy in HNSCC

Iowa City Va Medical Center, Iowa City IA

Investigators

Linked publications & trials

Abstract

Background and Innovation: The standard of care for locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) is surgery followed by post-operative radiotherapy (RT) or chemoradiotherapy (CRT). Unfortunately, patients have a high risk of locoregional failure after RT and up to 50% of patients will develop recurrent disease and/or second primary tumors. Additionally, treatment options are limited for locally recurrent and second primary tumors in a previously irradiated field. Therefore, there remains a significant need to identify novel therapeutic strategies in order to improve clinical outcomes for LA-HNSCC patients. RT can trigger anti-tumor immune responses and this may be exploited to improve the effectiveness of immunotherapy. While RT/CRT in combination with immunotherapeutic agents is a promising strategy conceptually, as more results are being reported from ongoing randomized phase 3 clinical trials, it is clear that targeting checkpoint inhibitors (e.g. anti-programmed cell death protein 1 [PD1]) is safe, but does not improve upon standard of care RT or CRT for LA disease. In this application we will test interleukin-1 (IL-1) ligands (IL- 1α and IL-1β) as an adjuvant to RT and CRT given the ability of IL-1 to target various aspects of anti-tumor immunity (dendritic, natural killer and T cells,) and thus be effective in both immunogenic and poorly immunogenic tumors. We hypothesize that IL-1 microparticle (IL-1MP)-based immunotherapy will trigger an anti-tumor immune response and improve durable response rates to RT/CRT for HNSCCs. Significance and Impact to Veterans Healthcare: Data from the Surveillance, Epidemiology and End Results (SEER) cancer registry show that HNSCCs are almost twice as common (6%) in Veterans as in non- Veterans (3%). Because of the high co-morbidity and overall poorer level of health seen in VA patients, conventional chemotherapy is difficult and, in some cases, not appropriate for many VA patients. However, immunotherapy-based strategies are highly suitable options for VA patients given the more favorable toxicity profile compared to other chemotherapy strategies and the remarkable durable responses that can be triggered. Path to translation/implementation: Overall if our strategy of IL-1MPs in combination with RT/CRT is successful, we will proceed with GLP toxicity studies and develop plans for GMP manufacturing for the IL- 1MPs. We believe that our combined strategy is a highly promising approach which may lower the risk of locoregional recurrences and second primaries, and target distant tumors which will improve overall survival outcomes in LA-HNSCC patients.