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High Throughput Profiling of the In Vivo Tumor Neo-antigen Specific Antibody Reactivity Landscape using PhIP-Seq

Award Number: R03CA304848
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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High Throughput Profiling of the In Vivo Tumor Neo-antigen Specific Antibody Reactivity Landscape using PhIP-Seq - Project Summary The overall goal of this explorative pilot project is to determine whether a recently developed systems immunology technique called PhIP-Seq can be applied to improve melanoma tumor specific antigen discovery and validation as well as to develop humoral responses as biomarkers for immune recognition of tumors. Identifying bona fide immunogenic tumor “neoantigens” is critical to the continued development and refinement of immunotherapy approaches to cancer. While new DNA sequencing technologies and bioinformatics tools have increased the speed at which tumor genomes can be sequenced and potential neoantigen creating mutations can be pinpointed, methods to validate candidate tumor antigens have lagged behind. Current neoantigen validation methods often involve time consuming and low throughput screening of individual peptides using primary cells in tissue culture, which sharply limits the scale and pace of the process. PhIP-Seq is designed to interrogate antibody binding specificity against every potential tumor antigen simultaneously, rapidly, and at large scale using biological primary samples with higher sensitivity than is achievable with ancestral technologies. By using modified phage display libraries coupled to deep sequencing and bioinformatic analysis PhIP-Seq has the potential to screen hundreds of human or animal model serum samples per experiment for antibody binding to up to hundreds of thousands of potential tumor neoantigens. This method can therefore use antibodies in a high throughput manner to simultaneously identify and validate immunogenic neoantigens and then monitor those responses over time. In AIM1 we will use PhIP-Seq to profile spontaneous neoantigen antibody reactivities in genetically defined mouse models of melanoma with or without pharmacologic therapies to explore how targeted and conventional chemotherapies alter the neoantigen antibody recognition profile. The use of genetically identical inbred animals will allow for the quantitative comparison of PhIP-seq determined humoral immune responses against the same tumor across many individuals with genetically identical immune systems, something which cannot be accomplished using human patient samples. In AIM2 we will use primary human melanoma patient material to define spontaneous antibody responses against private and public human melanoma neoantigens.


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: 2026 ( Subtotal = $155,500 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Biology Research	000	1	9/22/2026	NEW	$155,500
														Subtotal = $155,500

Grand Total All Awards = $155,500

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High Throughput Profiling of the In Vivo Tumor Neo-antigen Specific Antibody Reactivity Landscape using PhIP-Seq

Award Number: R03CA304848

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/21/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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