# Immunotherapeutic responses to neoantigens in head and neck cancer

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2020 · $578,036

## Abstract

PROJECT SUMMARY
In this application, we have assembled a multidisciplinary team to execute an integrated mechanistic and
translational program to defining neoantigen biology in head and neck squamous cell carcinomas (HNSCC).
Despite advances in multimodality treatment, a significant number of HNSCC patients suffer from recurrences
and distant metastasis. With recent advances in genomics driven oncology and immunotherapeutics, the
outcomes for afflicted HNSCC patients are likely to dramatically improve. However, there is an essential need
for a better understanding of HNSCC neoantigen biology as these tumor specific antigens are the final
common targets for immunotherapy. To address this key issue in immunotherapeutics, the work we propose
will directly address the NIDCR RFA on “Neoantigen-Based Therapeutic Targeting of Head and Neck Cancers”
by completing coupled mechanistic and translational studies. Supporting data provide a strong foundation in
which to pursue the proposed work and include intriguing findings regarding neoantigen biology in our high-
fidelity mouse models of HNSCC, novel clinical trial specimens in previously untreated patients and
immunophenotyping approaches in difficult to treat recurrent and/or metastatic HNSCCs (RM HNSCC). The
mouse oral carcinoma (MOC) model that we developed displays strong conservation to human HNSCC in its
carcinogen origin, in vivo biology and response to anti-PD1 checkpoint blockade and represents a platform for
mechanistic translational studies. Focusing on the MOC22 model, we identified this tumor line to possess both
an endogenous retroviral expressed antigen (p15E) and a mutated ICAM1 (mICAM1) gene that yields a
neoantigen. Antigen specific T cells for both of these antigens are present in growing MOC22 tumors.
Importantly, specific vaccination experiments result in response for both antigens but surprisingly only the
mICAM1 neoantigen provided protection from MOC22 tumor growth. These data have important implications
for neoantigen biology highlighting the need to not only identity neoantigens but also to define induced
responses in T cells. Coupled with these mechanistic approaches, we have initiated a novel neoadjuvant
pembrolizumab clinical trial that has shown surprising clinical results and highlights this approach as an ideal
setting in which to address neoantigen biology. Finally, we have immunophenotyped RM HNSCC tumor
samples towards understanding the low 15-20% response rates to anti-PD1 therapy. These supporting data
will be used to interrogate neoantigen mechanistic studies in the MOC model, define neoantigen landscapes in
neoadjuvant pembrolizumab treated samples using novel screening methodologies and define single cell RNA-
Sequencing transcriptome in antigen specific T cells. Finally, we will further expand on reports of increased
mutational burdens in the RM HNSCC setting to define whether this translates into neoantigen reactivity and
the associated T cell transcriptome. In co...

## Key facts

- **NIH application ID:** 9888974
- **Project number:** 5R01DE027736-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Ravindra Uppaluri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $578,036
- **Award type:** 5
- **Project period:** 2018-04-11 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888974

## Citation

> US National Institutes of Health, RePORTER application 9888974, Immunotherapeutic responses to neoantigens in head and neck cancer (5R01DE027736-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9888974. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*