SNAF Identifies Splicing Antigens to Help Expand Cancer Immunotherapy Potential

A novel computational tool called Splicing Neo Antigen Finder (SNAF) could help bring cancer immunotherapy to a wider range of patients, according to a study published in Science Translational Medicine. Developed by a team from Cincinnati Children’s and the University of Virginia, SNAF has already demonstrated its ability to identify shared immunogenic targets across diverse cancers, potentially paving the way for highly targeted cancer treatments.

SNAF operates by uncovering neoantigens resulting from post-transcriptional modifications, particularly splicing errors, which were previously underutilized. The tool utilizes artificial intelligence to predict immunogenic peptides recognized by T cells and novel proteins with altered extracellular components targeted by B cells. This dual approach aims to create comprehensive immunotherapies engaging both arms of the adaptive immune system.

Significantly, SNAF's predictions have highlighted splicing neoantigens' correlation with patient survival and responses to immunotherapy in melanoma cases. The prediction of SLC45A2 as a promising target due to its high tumor specificity and immunogenicity showcases the tool's potential impact.

Furthermore, the team using the B cell focused SNAF-B has identified a novel class of tumor-specific extracellular neo-epitopes called ExNeoEpitopes. These ExNeoEpitopes hold promise for developing monoclonal antibodies and CAR-T cell therapies.

"The implications of this discovery are significant," says H. Leighton Grimes, a co-author of the study. "By identifying shared splicing neoantigens present in up to 90% of cancer patients, SNAF not only presents new targets for therapy but also challenges and expands our understanding of cancer biology."

"This is only the beginning," says Tamara Tilburgs, co-corresponding author. "The SNAF workflow’s flexibility means it can be continuously adapted as we make further inroads into understanding and combating cancer."