July 23, 2024

Research Tool SNAF Revolutionizes Search for Cancer Immunotherapy Targets

A groundbreaking computational tool called the Splicing Neo Antigen Finder (SNAF) has the potential to expand the reach of cancer immunotherapy to a wider range of patients, according to a study published in Science Translational Medicine. Developed by a team of researchers from Cincinnati Children’s and the University of Virginia, SNAF has already helped identify shared immunogenic targets across different types of cancer, paving the way for highly targeted cancer treatments.

The study, led by Guangyuan Li, Ph.D., and Nathan Salomonis, Ph.D., from the Division of Biomedical Informatics at Cincinnati Children’s, has uncovered the significant implications of SNAF’s discovery. H. Leighton Lee Grimes, Ph.D., co-author of the study and director of the Cancer Pathology Program at Cincinnati Children’s, highlights how the identification of shared splicing neoantigens present in up to 90% of cancer patients not only reveals new therapeutic targets but also expands our understanding of cancer biology.

Traditional immunotherapy approaches focus on targeting neoantigens produced from genetic mutations, benefiting only those with a high mutational burden. However, SNAF seeks to broaden the scope of immunotherapy by identifying neoantigens resulting from post-transcriptional modifications, specifically splicing errors, which have been largely unexplored until now.

Leveraging artificial intelligence techniques, SNAF predicts immunogenic peptides that can be recognized by T cells and new proteins with altered extracellular components that can be targeted by B cells. This dual approach is crucial in developing comprehensive immunotherapies that engage both arms of the adaptive immune system. By cataloging all potential neoantigens generated from alternative mRNA pathways, the research team discovered a correlation between the abundance of splicing neoantigens and patient survival and responses to immunotherapy in melanoma patients.

One promising target prediction, SLC45A2, stands out due to its high tumor specificity and immunogenicity.

In addition to T-cell neoantigens, the researchers have also discovered a novel class of tumor-specific extracellular neo-epitopes called ExNeoEpitopes, using their B-cell focused pipeline, SNAF-B. These ExNeoEpitopes hold great promise for the development of monoclonal antibodies and CAR-T cell therapies.

This breakthrough is just the beginning, says Dr. Tamara Tilburgs, co-corresponding author and researcher in the Division of Immunobiology. The flexibility of the SNAF workflow allows for continuous adaptation as scientists gain deeper insights into cancer and develop better strategies to combat it.

Dr. Salomonis and his team are currently applying these tools to the most challenging-to-treat cancers to identify optimal therapy targets and gain a better understanding of their single-cell origins.

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