# Identification of splice variant derived neo-antigens in head and neck squamous cell carcinoma as targets for tumor vaccine therapy

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $235,417

## Abstract

Title: Identification of splice variant derived neo-antigens in head and neck squamous cell carcinoma
as targets for tumor vaccine therapy
Abstract
Immune checkpoint inhibitors (ICI) were recently FDA approved for first line treatment of recurrent and
metastatic head and neck squamous cell carcinoma (HNSCC). However, response rates to ICI in HNSCC are
less than 20%. Tumor specific neoantigens predict response to ICI therapy, and these immunogenic
neoantigens represent ideal targets for vaccines to enhance ICI response. Alternative splicing events, which
are present and functionally active in HNSCC, represent an understudied source of tumor-specific protein
diversity and novel neoantigens. The goal of this work is to identify the potential for splice variant derived
neoantigens to elicit an immune response and serve as targets for tumor vaccine development. Using an
established computational pipeline, splice variant derived peptides will be predicted and prioritized. Then an
immunocompetent murine model of oral cancer will be utilized to evaluate the functional immunogenicity of
aberrant splicing variants. Splicing variant products that are able to elicit an immune response will then be
incorporated into a vaccine and evaluated for the ability to enhance response of oral cancer to immune
checkpoint inhibitors. Finally, immune response to splice variant derived human neoantigens will be evaluated
in oral cancer patients to establish the role for translation of such therapies to the clinic. The proposed work
has the potential to transform the landscape of tumor neoantigens in HNSCC to include previously
unrecognized splicing variants derived neoantigens. These splice variants occur at a higher prevalence than
somatic mutations, generate highly immunogenic protein products with more extensive sequence alteration
than mutations, and their derivative neoantigens represent ideal targets for tumor vaccine development. While
this work is focused in oral cancer, the role of splice variants on anti-tumor immunity can be expanded to
impact other heterogeneous solid tumors.

## Key facts

- **NIH application ID:** 10887314
- **Project number:** 1K08CA276999-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Theresa Guo
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $235,417
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887314

## Citation

> US National Institutes of Health, RePORTER application 10887314, Identification of splice variant derived neo-antigens in head and neck squamous cell carcinoma as targets for tumor vaccine therapy (1K08CA276999-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10887314. Licensed CC0.

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