SpliceIO™ a novel AI platform for the discovery of splicing-derived immunotherapeutic targets

Alternative splicing (AS) plays a critical role in generating tumor-specific neoepitopes targetable through an arsenal of immunotherapeutic modalities. Previous studies have demonstrated tumor-promoting activity deregulated AS isoforms and mutated factors, both which increase the yield neoepitope-encoding isoforms. Therefore, identification has potential to produce novel therapeutic targets, especially tumor types where deregulation is frequent, like breast cancer. SpliceIOTM Envisagenics’ AI platform for AS-derived neoepitope discovery. SpliceIO uses “predictive ensemble” approach uncover that are stably expressed located on extracellular membrane cancer cells. Using SpliceIO, we analyzed >10,000 RNA-seq samples from 5 patient cohorts covering subtypes as well 2,647 normal GTEx identify present transmembrane proteins. Here, experimental evidence SpliceIO-identified We validated RNA expression neoepitope-expressing transcripts cell lines, primary cells FFPE tissues using combination RT-PCR RNA-FISH. Further, confirmed neoepitope-containing at protein level western blotting proteomics. Interestingly, one such candidate endoplasmic reticulum overexpressed TNBC tumors. The specific isoform localized plasma cells, suggesting different splice can alter localization. This demonstrates utilizing identifying many more associated proteins targeting. computational approaches allows target discovery amenable targeted development treatment clinical care. Conflict interest: Other Substantive Relationships: All authors salaried employees Envisagenics.