High-throughput discovery of cancer-targeting TCRs
Lukas Bunse1, Edward W Green2, Michael Platten1
1German Cancer Research Center, DKFZ, Heidelberg, Germany; University Hospital Mannheim, Mannheim, Germany; University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
The high-throughput discovery of T cell receptors (TCR) enables us to follow the longitudinal course of tumor disease, to monitor immunotherapy-related repertoire alterations, and exploit TCRs for therapeutic use. Here we discuss state of the art and future experimental and computational strategies to dissect the hypervariable world of TCRs and their corresponding antigens in the context of cancer immunotherapy.
Insights
High-throughput T cell receptor (TCR) discovery aids in tracking cancer progression and monitoring immunotherapy. Future strategies will enhance understanding of TCRs and antigens for cancer therapy.
Area of Science:
- Immunology
- Oncology
- Bioinformatics
Background:
- T cell receptors (TCRs) are crucial for adaptive immunity and recognizing cancer antigens.
- High-throughput sequencing technologies have revolutionized the study of TCR repertoires.
- Understanding TCR-antigen interactions is key to advancing cancer immunotherapy.
Purpose of the Study:
- To review current and future experimental and computational methods for TCR and antigen discovery.
- To highlight the significance of TCR repertoire analysis in cancer immunotherapy.
- To discuss the therapeutic potential of engineered TCRs in cancer treatment.
Main Methods:
- High-throughput sequencing for TCR repertoire analysis.
- Bioinformatic algorithms for TCR-antigen prediction.
- In vitro and in vivo models for TCR functional validation.
Main Results:
- High-throughput TCR discovery enables longitudinal monitoring of tumor disease.
- TCR repertoire alterations can be tracked during immunotherapy.
- Engineered TCRs show promise for therapeutic applications in cancer.
Conclusions:
- Advanced TCR discovery and analysis are essential for personalized cancer immunotherapy.
- Integrating experimental and computational approaches will accelerate the development of TCR-based therapies.
- Future research should focus on dissecting TCR-antigen interactions for improved cancer treatment outcomes.


