Abstract 247: Identification of an ovarian cancer selective splice variant of mesothelin utilizing the Kiromic proprietary search engine CancerDiff

The advancement of cures for cancer needs the development of novel, more efficacious, and more specific immunotherapeutic approaches through the discovery of novel target candidates displaying differential expression between healthy and malignant tissues. CancerDiff is a proprietary software module for the identification of potential new immunotherapeutic cancer targets that originate from differentially expressed, alternatively spliced transcripts. When utilized to analyze Ovarian Cancer (OV) datasets, CancerDiff identified a selectively upregulated mesothelin (MSLN) splice variant translated into a protein isoform (IsoMSLN) bearing a distinct unique peptide absent in the canonical protein sequence. To validate this prediction and to confirm the upregulation of IsoMSLN in OV, datasets from publicly available proteomic repositories were searched for its unique signature peptide. In agreement with CancerDiff prediction, IsoMSLN peptide was detected in 71% of OV samples and 61% of adjacent normal tissues. Molecular modeling tools predicted this peptide to be part of the extracellular portion of the protein in an antibody accessible region. These results indicate IsoMSLN unique peptide as a suitable target for immunotherapy for OV cancer. Citation Format: Lucia Piccotti, Leonardo Mirandola, Maurizio Chiriva-Internati. Identification of an ovarian cancer selective splice variant of mesothelin utilizing the Kiromic proprietary search engine CancerDiff [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 247.