Immuno-Oncology Solutions

TCR Sequencing

T-cells are the core components of our adaptive immune system. Once activated, they can directly kill cells that are foreign (cytolytic T-cells) or perform helper function (helper T-cells) to activate B-cells to make antibodies against foreign antigen. The activation of T-cells involve recognition of MHC-peptide complex by the T-cell receptors (TCR). Humans carry >109 T-cells, each expressing a unique TCR. This highly diverse repertoire of T-cells has the ability to recognize peptides originating from foreign elements such as invading pathogens and cancer cells. Each TCR recognize peptides in complex with MHC proteins presented on the surface of antigen presenting cells. Productive T-cell activation results in the clonal expansion of a specific T-cell and this expansion can be accurately determined by TCR sequencing.

TCR profiling holds great potential not only for understanding the mechanisms of development of the normal immune response, but also in providing insights into disease mechanisms and development of new therapeutics and treatment modalities in infectious diseases, autoimmunity and in immuno-oncology. However identification of all potential clonotypes in a diverse repertoire of TCRs requires sensitive methods of detection. Next-generation sequencing (NGS) technologies have recently enabled accurate detection of TCRs, and in combination with other assays allow for the assessment of the TCR repertoire in patients- which in turn is a proxy for patient prognosis and response. At MedGenome, we provide TCR repertoire profiling using bulk input (from cells, RNA and FFPE tissue) using the SMARTer® TCR Profiling Kit (Takara Bio USA Inc) and single-cell inputs using the SMARTer single-cell TCR Profiling kit and the Chromium Immune Profiling solutions (10X Genomics). To learn more about the different applications and sample data generated using TCR Seq at MedGenome read the white paper..

Major Applications of TCR Repertoire Profiling

Figure 1. Overview of major applications of TCR Repertoire profiling in a) Therapeutics application: TCR Sequencing of lymphocytes to identify antigen specific TCRs to generate engineered T cells for adoptive cell therapy b) Diagnostics assay for clonality for auto immune disorders c) Treatment monitoring: to identify biomarkers of response.

Highlights of our services are:

  • Flexibility in input & wider dynamic range for assays
    • Per cell more copies of transcripts vs genomic DNA ( several copies vs 2 copies for genomic DNA)
    • Higher sensitivity in detecting in lower frequency TCRs ( found in healthy donor blood, PBMCs, spleen & lymph node)
    • Ease in detecting TCR transcripts from low quality and quantity of input ( samples stored under various conditions)
  • Accurate representation of expressed TCRs vs non-functional TCRs ( stop codons at the RNA level can be ruled out upon analysis )
  • Ability to extract TCR and other expression information ( transcriptome for functional state of T-cells )
  • Reduced Amplification bias
  • Improved ability to call novel and low frequency clonotypes

End-to-End Complete Service – TCR Workflow

TCR Library Prep, Sequencing, and Analysis Service Offerings

Source Library Prep Options Analysis Offering
  • Cells
  • Tissues
  • Blood
  • FFPE
  • Curls
  • Purified Total RNA
  • Takara SMARTer TCR alpha/beta Profiling Kit (Human, Mouse, custom species)
  • MedGenome FFPE TCR Profiling Library Prep (human)
  • MedGenome Gamma/Delta Profiling Library Prep (Human, custom species)
Standard Analysis
  • MiXCR Output file - Clonotype Frequency, Gene and Amino Acid Sequences
  • V J Gene Usage
  • Shannon's Diversity
  • V J Circos Plot
  • Spectratype Plot
  • Scatter Plot
  • Custom figures available upon request

In addition to the TCR Seq services, MedGenome offers advanced informatics solutions for TCR binding based prediction of immunogenic neoepitopes for cancer vaccine development using OncoPeptVACTM

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