Advance Precision Immuno-Oncology with Comprehensive TCR & BCR Sequencing

Discover how high-resolution repertoire profiling delivers a more complete, clinically actionable view of adaptive immunity in cancer trials.

Key Takeaways:

• Tumor-centric markers such as PD-L1 expression and tumor mutational burden offer only an indirect view of immunotherapy response, resistance, and durability.
• Comprehensive TCR and BCR sequencing provides a direct, quantitative readout of immune diversity, clonal expansion, and persistence, connecting immune dynamics to clinical outcomes.
• Published studies in CRISPR-edited TIL therapy and lifileucel show how repertoire profiling supports product characterization and regulatory-grade immune response monitoring.
• iRepertoire’s RepSeq® bulk, seven-chain sequencing and single-cell iPair™ solution give translational and clinical teams the depth and sensitivity needed to detect and follow therapeutically relevant clones.

Closing the Gap in Immuno-Oncology Biomarkers

Immuno-oncology has entered a precision era. As checkpoint inhibitors, cell therapies, and cancer vaccines move deeper into clinical development, the demand for biomarkers that explain response, resistance, and durability has never been higher. Yet widely used markers, such as PD-L1 expression or tumor mutational burden, often fail to fully predict outcomes. These measures describe the tumor, not the immune system responding to it. What is missing is a direct, quantitative readout of adaptive immunity itself: how many unique T and B cell clones are engaged, how they expand, and whether they persist long enough to impact clinical outcomes.

Comprehensive TCR and BCR sequencing addresses that gap. By measuring immune diversity, clonal expansion, and persistence, this approach gives translational teams a functional signal of therapeutic activity that tumor-focused assays cannot provide on their own.

The Missing Piece in Immuno-Oncology Biomarker Strategy

Current biomarker strategies lean heavily on tumor-centric signals. These are valuable, but they only offer indirect insight into how the immune system is actually responding to therapy. Immune repertoire profiling adds a functional dimension to biomarker programs by:

• Quantifying clonal expansion tied to antigen recognition
• Measuring immune fitness and diversity over time
• Tracking treatment-induced immune remodeling

A key consideration for study design is chain coverage. Limiting analysis to a single receptor chain restricts the biological story a dataset can tell. A comprehensive, multi-chain TCR and BCR repertoire profiling approach captures a fuller and more clinically actionable picture of adaptive immunity across a treatment course.

What TCR and BCR Sequencing Reveal

TCR sequencing captures specific T cell-mediated cellular immune responses, giving researchers the ability to track tumor-infiltrating lymphocytes (TILs), monitor clonal expansion following checkpoint blockade, and measure the persistence of infused cell therapy products over time.

BCR sequencing complements this with insight into humoral immunity, supporting identification of antigen-driven B cell responses, discovery of antibody-associated biomarkers, and evaluation of vaccine and immune memory responses.

Used together, TCR and BCR sequencing link immune dynamics directly to clinical outcomes rather than stopping at molecular correlates alone, helping teams build biomarker packages grounded in immune function.

Applying Comprehensive TCR and BCR Sequencing in Immuno-Oncology Clinical Trials

Two recent studies illustrate how this approach performs in active clinical programs.

CRISPR-Edited TIL Therapy in Metastatic Gastrointestinal Epithelial Cancer

In a first-in-human trial of a CRISPR-edited TIL product with CISH knockout, immune repertoire profiling confirmed polyclonality and neoantigen specificity of the cell product prior to infusion and enabled high-resolution tracking of tumor-reactive TCR clones before and after treatment.¹ This supported process control and product characterization while demonstrating the feasibility and safety of intracellular checkpoint targeting. The resulting immune biomarkers linked clonal expansion and persistence to clinical response and generated regulatory-grade immune monitoring data in a highly resistant cancer type.

Lifileucel TIL Therapy in Refractory Non-Small Cell Lung Cancer (NSCLC)

In a Phase 2 study of lifileucel in metastatic non-small cell lung cancer resistant to immune checkpoint inhibitor therapy, TCR repertoire profiling verified the polyclonal, tumor-reactive composition of the TIL product before infusion, quantified CD8+ and CD4+ effector/memory T cell diversity, and enabled molecular tracking of infused clones to assess persistence and durability.² Repertoire features were linked to therapeutic response in patients who showed resistance to anti-PD-1/PD-L1 therapy, offering correlates of durable response across molecular subgroups, and supporting biomarker-informed refinement of TIL manufacturing and patient selection.

Purpose-Built Immuno-Oncology Solutions

Clinical adaptive immune profiling calls for depth, sensitivity, and reproducibility together, without asking teams to trade one for another.

iRepertoire’s proprietary immune repertoire profiling platform delivers:

• Seven-chain TCR/BCR coverage for a complete view of adaptive immunity
• Ultra-sensitive detection of rare, clinically relevant clones
• RepSeq+® bulk and iPair™ single-cell sequencing solutions for translational and clinical-stage programs
• Intellimune™ data analysis services purpose-built for biomarker discovery, mechanism validation, and regulatory support

From early translational studies through late-stage clinical trials, immune repertoire profiling is becoming a foundational part of how immuno-oncology biomarker programs are built.

Conclusion

As immuno-oncology continues to advance, biomarkers need to reflect immune function alongside tumor features. Comprehensive TCR and BCR sequencing supply that connective signal, linking immune response to clinical outcome with the resolution and reproducibility that translational and regulatory teams require.

Explore how iRepertoire supports biomarker-driven immuno-oncology programs.