Utilising Multi-Omic Data to Drive Expansion of the Cancer Immunopeptidome

Jonathan Woodsmith, Phd (Indivumed)

Colorectal cancer (CRC) remains a significant global health challenge, necessitating innovative approaches to enhance our understanding of its immunogenicity and identify potential targets for immunotherapeutic interventions. Here we present a strategy leveraging multi-omic data and the use of high-quality tissue specimens to expand our knowledge of the CRC immunopeptidome.

Exploration of genomics, transcriptomics and proteomics datasets can increase the type of tumor associated antigens (TAAs) that can be identified. Here we aimed to elucidate the landscape of MHC-I TAA presentation of cryptic peptides expressed from lncRNAs in CRC. High-quality cancer and healthy tissue samples, collected with stringent protocols to preserve molecular integrity as well as cutting-edge multi-omic data, serve as the foundation for our investigation.

Initially we vastly reduced the search space of putative cryptic peptide expression by >95% through combining public databases with patient based rRNA depleted RNA-Seq data. Through stringent MHC-I immunoprecipitation followed by DIA LC-MS/MS, we could identify peptides both originating from the wild type proteins as well as revealing over 100 peptides predicted to originate from lncRNAs. Of these, approximately one third were presented only on tumor tissue, representing an extensive basis for bioinformatic and experimental characterization of this novel TAA space. Furthermore, these cryptic peptide TAAs showed differing degrees of patient overlap paving the way for precision immunotherapies tailored to specific patient groups.

Short Bio Jonathan Woodsmith:

Currently heading up Research & Development of biomarkers, signatures and therapeutic targets discovered utilizing Indivumed Therapeutics’ patient based multi-omic cancer database. Combining a background in both molecular and computational biology, Jonathan aims to drive forward cutting edge precision medicine approaches across oncology, with a long term goal of benefitting patients through better and more targeted treatments.

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Utilising Multi-Omic Data to Drive Expansion of the Cancer Immunopeptidome

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