Algorithms for HLA-e based cancer immunotherapy

Active Project Grant Awarded Last action

Award ID
R56CA308267
Recipient
Awarding agency
Obligated
$75,000

Award facts

Assistance listing
93.396 Cancer Biology Research
Completion date 14% complete
Place of performance
Baltimore, MD 21201, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Adoptive immunotherapy faces challenges due to limited cancer-specific targets. Proteoforms from structural variations and microproteins derived from unannotated open reading frames offer valuable neoantigen resources for tumor-specific immunotherapies. Human leukocyte antigen (HLA) presents neoantigens to cytotoxic t cells, triggering immune responses to eliminate cancer cells. Unlike polymorphic classical hlas (HLA-a, -b, -c), HLA- e exists in two predominant forms and presents tumor-specific antigens to HLA-e-restricted t cells, serving as broadly expressed targets for t cell-based therapies. While computational prediction of peptide-HLA (phla) binding can accelerate neoantigen discovery, reliable peptide-HLA-e binding prediction remains a challenge due to limited interaction data. We previously developed proteogenomic variant callers to identify proteoforms involved in organogenesis and tumorigenesis. Using an immunoprecipitation-mass spectrometry (IP-MS) approach, we profiled HLA-e-bound peptides and identified medulloblastoma-specific antigens. Additionally, we developed a simplified model using ESM3 embeddings to predict peptide-HLA-e bindings, demonstrating its effectiveness in capturing the features of HLA-e binders. These efforts demonstrate the feasibility of combining proteogenomics and computational predictions to identify HLA-e-presented neoantigens. With these efforts, we aim to develop bioinformatics algorithms to mine neoantigens that can be targeted by HLA-e based cancer immunotherapies. Our specific aims are: 1) develop a computational suite to identify tumor-specific proteoforms and microproteins; 2) develop a more powerful computational model for HLA-e binding prediction; and 3) identify HLA-e restricted neoantigens and evaluate HLA-e based t cell immunotherapy. Successful completion of the specific aims of this proposal will establish an innovative approach for identifying neoantigens and developing universal HLA-e-based cancer immunotherapies.

Quick answers

Who received award R56CA308267?

R56CA308267 was awarded to University Of Maryland, Baltimore by National Cancer Institute (National Institutes of Health) on September 1, 2026.

How much is award R56CA308267 worth?

$75,000 has been obligated on R56CA308267.

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