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

Award Number: K08CA276999
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $235,417 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Research Manpower	000	2	7/28/2025	NON-COMPETING CONTINUATION	$235,417
														Subtotal = $235,417

Issue Date FY: 2024 ( Subtotal = $235,417 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Research Manpower	000	1	8/21/2024	NEW	$235,417
														Subtotal = $235,417

Grand Total All Awards = $470,834

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

Award Number: K08CA276999

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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