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Research & Application

Applications

Discovery the versatility of immune repertoire analysis

The added value of imune reportoire analysis at all stages of biomedical research

Understanding the immune system is central to several of the most important and therapeutically relevant developments in modern medicine. Immune repertoire analyses provide in-depth understanding of the immune system and consequentially every stage of biomedical research.

Analysis
Treatment monitoring
Clinical

The severe, and sometimes unexpected, adverse effects that may come with immunotherapy, transforming treatment monitoring into a matter of paramount importance. B and T cell repertoires can be seen as a fingerprint of the immune response, turning the dynamic changes thereof into promising biomarkers to monitor immunomodulatory therapies.

Multi-model treatment exploration
Clinical

Substantial effort is put into the exploration of multimodal treatment approaches to increase the effectiveness and minimize the adverse effects of immunotherapies. Repertoire sequencing can be exploited to track clones over time, allowing for the comparison between treatment arms and herewith obtain mechanistic insights into differences in therapeutic efficacy.

Patient stratification
Clinical

There is a great need for biomarkers to predict, prior to treatment, which patients are likely to experience treatment benefit. A growing number of immune repertoire features (e.g. T cell repertoire diversity and clonal expansion) is found to correlate with treatment response, showing its importance for biomarker development

Cancer vaccines efficacy evaluation
Clinical

Therapeutic cancer vaccines are considered to be a very promising cancer treatment but have so far demonstrated only modest therapeutic effects in clinical trials. To enhance the vaccine-induced immune responses and treatment efficacy, several treatment strategies are currently being validated in preclinical and clinical trials. The tumor infiltrating lymphocyte (TIL) content after vaccination and the T cell overlap between repertoires pre- and post-vaccination have been found to associate with overall survival. Repertoire sequencing enables accurate and quantitative assessment of (TIL) clone repertoires over time, allowing for better and faster vaccine development.

Immune recovery monitoring
Clinical
Translational

Hematopoietic stem cell transplantation (HSCT) is an effective, but invasive, treatment that is increasingly applied for a variety of cancers and congenital immunodeficiency disorders. It has shown promising, durable responses in some patients, but remains a dangerous procedure with many potentially life-threatening complications. Assessment of the TCR repertoire in HSCT recipients has shown to provide crucial information required to improve patient care. Spectratyping, currently the gold standard for TCR repertoire assessment, is notably limited by its resolution and unable to provide data on the nucleotide level. The application of repertoire sequencing can provide novel insights into immune recovery in these patients and help us to better understand clonotype dynamics during clinically relevant events, such as infections, oncologic relapses and graft-versus-host disease.

Biomarker discovery
Basic
Clinical
Translational

Due to the dynamic nature of the immune system that immunomodulatory drugs aim to modify, immunotherapies have often been associated with severe, and sometimes unexpected adverse effects. The information that is captured in repertoire sequencing data drives the translation of biological data into predictive biomarkers, to better respond to (individual) patient responses, further personalizing medicine.

Acquisition of BCR genes for CAR-T therapy
Clinical

Chimeric antigen receptor (CAR) proteins contain an antibody-derived fragment that is responsible for tumour (antigen) recognition. The identification of an antibody fragment that binds your specific antigen of interest poses a major challenge. The circulating antibodies in a humans body encompass B cells expressing receptors with a broad range of binding affinities to specific antigens, and provide a pool of antibodies possessing the desirable characteristics for CAR-T cell therapy. High-throughput repertoire analyses are particularly suited for the identification of CARs for the development of optimized CAR-T cell therapies.

Neoantigen-based cancer immunotherapy
Basic

Immunotherapies that target neoantigens (i.e., pieces of endogenous cancer proteins presented on the surface of tumour cells), hold great promise as cancer-specific markers. Targeting neo-antigens enables immune cells to distinguish cancerous from healthy cells, therefore reducing the risk of inducing an autoimmune response. Neoantigens are, however, in large part patient-specific and therefore require a fundamentally different target discovery approach. Repertoire sequencing can reveal the mutational spectrum of individual tumours with unprecedented precision and speed, allowing for the swift identification of patient-specific epitopes. These unique targets can be exploited to design personalized immunotherapy programs that boost mutation-specific adaptive immunity.

Immune repertoire mining: by-passing the screening process
Basic

Continuous pathogen evolution makes rapid discovery of monoclonal antibodies with distinct affinities and specificities of great importance for treatment and disease control. The traditional workflow of antibody discovery typically entails laborious screening processes to identify antibodies with the right antigen specificity. However, deep sequencing data has enabled high-throughput identification of high affinity antibodies based on solely clone frequencies, this way by-passing the screening step and significantly speeding up the discovery phase.

Efficient screening of human antibodies
Basic

Screening of large antibody libraries by ribosomal, phage, bacterial or yeast display is widely employed for the isolation of antibodies. Repertoire Sequencing provides an accurate, sensitive and high-throughput solution for the detection of enriched antibodies that bind an antigen of interest and serve as potential drug candidates.

Target discovery
Basic

The discovery of promising drug targets is an expensive and laborious process. Repertoire Sequencing expands biological investigations beyond studying single lymphocyte receptors to a comprehensive analysis of the immune repertoire as a whole in a systematic way, thereby accelerating the drug discovery process.