Immunopeptidome Profiling Unleashes the Power of Personalized Immunotherapy

Immunopeptidome Profiling Unleashes the Power of Personalized Immunotherapy

In our previous blog, ‘Cracking the Immune Code’, we explored the relatively new field of immunopeptidomics – the study of the repertoire of peptides presented by cells that play a vital role in directing and regulating the immune response.

 

Immunopeptidome profiling at this scale provides a detailed snapshot of what the immune system reacts to within a particular tissue. This has important implications for understanding and treating cancer, autoimmune conditions and infectious diseases and underpinning the development of novel vaccines.

 

At Biognosys, our mass spectrometry-based TrueDiscovery™ platform offers an Immunopeptidome Profiling service that can identify more than 10,000 HLA or MHC Class I and Class II immunopeptides using 15 mg of tissue or less.

 

Here, we take a closer look at some of these exciting new technology applications and how you can bring the power of immunopeptidomics to your own R&D pipeline.

 

Immunopeptidome Profiling for Next-generation Cancer Immunotherapy

 

Oncology is one area where insights into the immune system have already led to new treatments and transformed outcomes for patients through novel therapies that harness the immune system’s power.

 

Since the first antibody therapy approvals in the early 2000s, cancer immunotherapy1 has progressed rapidly and generated significant benefits for patient survival and quality of life.

 

However, the outcome of immunotherapy often remains somewhat uncertain as the complexities of how cancer cells interact with the immune system are yet to be fully understood.

 

Immunopeptidomics can help here by screening tumor antigens at unprecedented depth and scale, providing information and biomarkers on the molecular basis for treatment response (or non-response), and identifying new therapeutic targets.

 

Immunopeptide profiling can advance our understanding of cancer immunology. Furthermore, it can drive forward precision immunotherapy in oncology by identifying tumor-specific neoantigens resulting from mutations within cancer cells.

 

These neoantigens can be used to guide tailored treatment approaches for cancer, such as through the development of personalized cancer vaccines2.

 

Immunopeptide profiling can also find new biomarkers for patient stratification. For example, it could identify patients who are more likely to benefit from immunotherapy because their cancers are highly dissimilar to their tissues3.

 

Demonstrating the Power of Immunopeptide Profiling in Lung Cancer

 

We recently demonstrated the power of our Immunopeptidome Profiling solution by generating MHC immunopeptide profiles from needle biopsies from 12 patients with lung cancer and matched healthy tissue. We were able to identify more than 11,000 Class I and more than 9,000 Class II immunopeptides on average from each sample.

 

A significant number of these immunopeptides were upregulated in the tumor samples. In addition, many corresponded with known cancer-specific proteins.

 

This included Matrix Metalloproteinase 11 (MMP11), a critical remodeler of the cancer microenvironment and known therapeutic target in lung cancer. Other identified candidates include the cell cycle checkpoint kinase CHEK1 and the proto-oncogene SET, which is highly overexpressed in lung tumors.

 

The power of our Immunopeptidome Profiling solution is also highlighted by our strategic partnership with Indivumed, developers of the world’s leading platform for precision oncology.

 

Combining our robust Immunopeptidome Profiling solution with Indivumed’s global multi-omics database and in-depth analytical insights has enabled fresh biological insights that have enhanced their immuno-oncology research and drug discovery efforts.

 

Towards a Map of the Human Immunopeptidome

 

Beyond oncology, immunopeptidomics has the potential to help us better understand – and leverage for treatment – the function of the immune system in a range of disease states.

 

As technology advances, immunopeptidome-wide association studies (IWAS)4, analogous to genome-wide association studies (GWAS), could be applied to discover the differences in immune profiles of different patient cohorts.

 

Information gleaned from these studies could improve our understanding of the disease process in autoimmune conditions such as type 1 diabetes and rheumatoid arthritis. It could help predict an individual’s risk of developing a disease or response to treatment.

 

Immunopeptidomics insights can also guide the design of new therapeutics, including vaccines. During an infection, peptides from the invading pathogen are presented on the surface of infected cells to alert T cells to the intruder.

 

Surveying these peptides is a powerful tool for identifying new vaccine targets. Immunopeptide-based research towards new bacterial vaccines5 is ongoing and could be helpful in the arsenal against antimicrobial resistance6.

 

When integrated with genomic information, immunopeptidomics has even greater potential for drug discovery. The emerging field of proteogenomics7 – a multi-omics approach that includes mass spectrometry-based proteomics, genomics, and transcriptomics – can further enhance the discovery of new immunogenic peptides and new therapeutic targets.

 

Accelerate Your Immunotherapy Research

 

Mass spectrometry is currently the only technology that can reliably capture immunopeptide profiles at scale.

 

Whatever your immune profiling needs, our in-depth Immunopeptidome Profiling solution can help. Our optimized high-throughput workflow offers reliable identification and quantification of 10,000 immunopeptides from just 10-15 mg of tissue. It can be used for neoantigen discovery for immuno-oncology applications and research into autoimmune conditions, infectious diseases, and vaccines.

 

We can support your research every step of the drug development pathway, from initial discovery right through to clinical trials. Moreover, our services are GLP certified and GCP compliant, generating regulatory-grade data to support market authorization.

 

Get in touch to find out how we can help you accelerate your immunotherapy research.

 

References:

  1. https://www.nature.com/articles/s41577-020-0306-5
  2. https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-019-0666-2
  3. https://www.cell.com/cell-systems/fulltext/S2405-4712(19)30307-2
  4. https://www.genome.gov/genetics-glossary/Genome-Wide-Association-Studies
  5. https://www.cell.com/trends/microbiology/fulltext/S0966-842X(21)00121-9
  6. https://www.who.int/health-topics/antimicrobial-resistance
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392723/
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