Immunopeptidome Profiling Archives - Biognosys

Our collaborator, GreyWolf Therapeutics, has uncovered the effect of aminopeptidase ERAP2 inhibition for generating the de novo antitumor T-cell responses, thereby overcoming the resistance mechanism for current immune-oncology therapy.

Learn more about leveraging our TrueDiscovery® immunopeptidomics CRO services to overcome the challenges in immune-oncology.

Disclaimer: The contact information provided for poster download will also be shared with GreyWolf Therapeutics

 

Endoplasmic reticulum aminopeptidase 1 (ERAP1) plays a central role in the modulation of the immunopeptidome
in all human cells and in N-terminal trimming of immunopeptides to 9-10mers in the endoplasmic reticulum
(ER) for loading and presentation via major histocompatibility-1 (MHC-1).
Therapeutic inhibition of ERAP1 provides a mechanism to increase the visibility of previously hidden neoantigens and
the visibility of the tumor to the immune system.
Discover how our TrueDiscovery Immunopeptidome Profiling services enabled Grey Wolf to assess immunomodulation following ERAP inhibition.

Understanding and targeting the immunopeptidome is often critical for advancing immuno-oncology and autoimmune therapies, but researchers commonly encounter challenges related to sensitivity, reproducibility, and limited sample availability. Biognosys’ advanced immunopeptidome profiling services and tailored bioinformatics enable precise identification and quantification of MHC-presented peptides in human and pre-clinical species using minimal sample input. With extensive experience in TCR-T therapies, cancer vaccines, and immunomodulatory treatments, Biognosys is your trusted partner in driving innovation in precision therapies.

 

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Therapeutic peptide-based vaccination is a promising strategy for cancer immunotherapies. The identification of tumor-specific antigens is key to developing therapies. Mass spectrometry has emerged as the primary technique for the identification of peptides presented on human leukocyte antigen (HLA), i.e., immunopeptides. While tremendous progress has been made, the analysis of immunopeptides remains challenging. This is especially true in a clinical context where tissue material is scarce, often limited to a handful of biopsies, with amounts below 20mg. Here, we introduce a workflow that allows deep immunopeptidomics profiling of clinically relevant samples.

Biognosys, in partnership with PreOmics, showcases the latest advances in mass spectrometry–based plasma proteomics and immunopeptidomics. A pilot study using P2 Plasma Enrichment Technology explores circulating biomarkers predictive of treatment response in breast cancer, complementing insights from Olink. Two immunopeptidomics studies with Spectronaut 20 reveal kinase-regulated tumor antigens in chronic myeloid leukemia and show how ERAP1 inhibition reshapes the HLA-B*27:05 immunopeptidome in autoimmunity. Join us to explore these cutting-edge technologies and their translational impact on biomarker discovery.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) plays an important role in shaping the immunopeptidome across all human cells by trimming peptide precursors prior to loading onto major histocompatibility complex class I (MHC-I) molecules in the endoplasmic reticulum (ER). This process modulates the repertoire of peptides available for recognition by CD8+ T cells, directly influencing immune surveillance. Therapeutic inhibition of ERAP1 modulates neoantigen repertoire driving the presentation of different cancer antigens, thereby triggering functional anti-tumor T-cell responses and opening new target spaces for TCR-based therapies.

 

To study immunopeptides bound to MHC-I or MHC-II, discovery mass spectrometry (MS) is essential for unbiased identification of the presented antigen repertoire. While discovery MS is typically semi-quantitative, precise characterization of antigens of interest requires accurate estimation of copy number per cell, which provides valuable insights into antigen abundance and potential immunogenicity. However, current methodologies for measuring these antigens are limited by low sensitivity, making it challenging to quantify immunopeptides from complex biological samples.

Major histocompatibility complex (MHC) molecules play a pivotal role in orchestrating immune responses by presenting antigenic peptides derived from both self and foreign proteins. In cancer, understanding the repertoire of tumor-associated antigens displayed by MHC molecules is critical for revealing how the immune system detects and responds to malignant cells. The identification of neoantigens—peptides arising from tumor-specific somatic mutations—has become a central focus in immunopeptidomic research.

A major challenge in systematic immunopeptidomics remains the high input material typically required for robust analysis.To address this, we developed a semi-automated workflow (Fig. 1) optimized for the reliable identification and quantification of immunopeptides from limited cell numbers and small tissue biopsies. We further assessed the compatibility of this workflow with allele-specific HLA enrichment. Finally, we tested its performance on peripheral blood mononuclear cells (PBMCs), a clinically relevant and commonly used sample matrix, demonstrating its utility in translational and clinical research settings.

Modulating the immune system in the fight against cancer has become a fast growing field with notable success. The study of presented peptides on major histocompatibility complex (MHC), i.e., immunopeptides, in disease and healthy tissues have become cornerstones of immuno-oncology. Mass spectrometry is the method of choice for the study of immunopeptides. With the progression from cell lines and model systems’ basic research to clinical application, the need for robust workflows for analysis of biopsies. The minute nature of needle biopsies require small scale and single preparation sample preparation and MS acquisition. We present progress in sample preparation downscaling and its application to clinically relevant sample types.

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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