T Cell Receptor (TCR) Repertoire Analysis for Biomarker Discovery

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

T cell receptor (TCR) is an essential molecule for T cells to recognize neoantigens in tumors. TCR diversity has previously been correlated with clinical outcomes for checkpoint inhibitor immunotherapy. Monitoring the high amplification of TCR clones may help to assess the status of an immune response. Next-generation sequencing (NGS) technology provides a feasible method to simultaneously identify a large number of TCR clones and is widely used in the clinic for TCR repertoire analysis.

With Ph.D. level scientists and extensive experience in TCR repertoire analysis for Biomarker Discovery, Creative Biolabs is dedicated to serving every unique need of our clients in biomarker development by providing custom services to meet our clients' R&D timeline and budget.

TCR Repertoire: Source of Biomarkers for Immune Monitoring

The extraordinary success of anticancer immunotherapies targeting the immune checkpoint molecules has strengthened awareness of the essential role of the immune system in eradicating tumors. Immunotherapeutic strategies have been shown to activate the immune system and boost tumor-specific immune responses, but not all patients show clinical improvement. Sensitive methods to monitor the immune response after treatment and biomarkers predicting clinical benefit are scarce. In the last few years, the ability to predict whether a patient will respond or become resistant to immunotherapy is increasingly benefiting from biomarkers that reflect the state of the T cell repertoire. Key factors that may contribute to a better understanding of the impact of immunotherapies on the patient adaptive immune system appear to be TCR diversity and clonality. As the mechanistic basis of adaptive cellular antigen recognition, TCRs encode clinically valuable information that reflects prior antigen exposure and potential future response. Advances in deep repertoire sequencing greatly promote the analysis of enormous TCR diversity for the discovery of clinical biomarkers.

Table 1. TCR repertoire metrics used as biomarkers in major checkpoint blockade immunotherapy studies.

Disease	Checkpoint Blockade Immunotherapy	TCR Repertoire Metrics as Biomarkers
Melanoma	CTLA4	Richness, Shannon diversity index, Pielou's evenness index
Melanoma, prostate	CTLA4	Top 25th percentile clonotypes, Morisita's distance
Melanoma	PD-1	Shannon entropy, 1-normalized entropy
Urothelial	PD-L1	Shannon entropy, 1-normalized entropy
Non–small-cell lung cancer	PD-1	1-normalized entropy
Melanoma	PD-1/CTLA4	1-normalized entropy
Melanoma	CTLA4	Richness, evenness index
Melanoma	PD-1/CTLA4	Diversity evenness score (DE50)
Pancreatic ductal	CTLA4	Morisita's distance, 1-normalized entropy
Adenocarcinoma	CTLA4	Morisita's distance, 1-normalized entropy
Melanoma	PD-1/CTLA4	Shannon
Melanoma	PD-1/CTLA4	Entropy, TCR clonality
Prostate	CTLA4	Shannon entropy, 1-normalized entropy
Non–small-cell lung cancer	PD-1/PD-L1	Shannon entropy, 1-normalized entropy
Melanoma	CTLA	1- Pielou's Evenness, Morisita's distance
Clear cells, melanoma, prostate	CTLA	Shannon entropy, TCR Convergence

TCR Repertoire Analysis for Biomarker Discovery at Creative Biolabs

Creative Biolabs has long-term devoted to biomarker development for immune monitoring purposes. With years of experience, our scientists have developed an advanced Immune Monitoring Platform for biomarker discovery to boost our clients' research and project goals. Our R&D scientific team has conducted many TCR repertoire analysis projects, including TCR repertoire analysis at the single-cell level. Both bulk samples (such as tissues or peripheral blood) or sorted cell subsets could serve as a biomarker to monitor or to predict the responses of patients to treatment. The results of several projects revealed that a higher TCR repertoire diversity in the blood of patients was linked with longer progression-free survival (PFS), while low diversity is associated with poor prognosis. Increasing evidence that TCR repertoire diversity can be a predictive biomarker of immune responses in cancer patients.

Workflow

T Cell Receptor (TCR) Repertoire Analysis for Biomarker Discovery

TCR Repertoire Analysis Including but Not Limited to

Alignment analysis
Frequency analysis of VDJ gene usage
CDR3 length analysis
Diversity Analysis
Saturation analysis
Analysis of unique sequences and common sequences in multiple samples
CDR3 variable region analysis

As many new combination therapies are developing, TCR repertoire analysis should be studied, alone or in combination with other immune parameters, as a source of biomarkers for immune monitoring. Many years of experience in TCR repertoire analysis for biomarker discovery have led to a large number of successes. Creative Biolabs is pleased to use our extensive experience and advanced platform to offer the best service to satisfy each demand from our clients. Please feel free to contact us for a detailed quote and further discussion with our scientists.

Reference

Aversa, I.; et al. Molecular T-cell repertoire analysis as source of prognostic and predictive biomarkers for checkpoint blockade immunotherapy. International journal of molecular sciences. 2020, 21(7):2378.