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A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Profiling targets and potential target pairs of CAR-T cell therapy in clinical trials
Daiyan Zhang1, Liyang Lyu1, Shuo Han2
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Abstract:
Since the approval of the first chimeric antigen receptor (CAR)-T product in 2017, the number of new CAR-T clinical trials worldwide exceeds 100 per year. 1649 clinical studies have been conducted to explore possible future clinical applications of targets or target pairs through different biotechnologies. In this study, we aim to take a data-driven analytical approach to explore potential dual-target pairs based on clinical trial information. We screened 1283 non-withdrawal interventional CAR-T clinical trials spanning 96 different targets and 74 target pairs from clinicaltrials.gov. Through the Circos plot and temporal network plots, the information between targets and indications was visualized. Based on the assumption that two targets of a target pair must target the same indication, five new target pairs were inferred, including CD19/CD7, CD19/CD5, CD19/CD37, and CD19/BAFFR and validated by expression pattern, literature and patent information. This study provides novel support for target profiling of CAR-T from the perspective of clinical trials and also provides a reference for researchers and developers to select new targets or target pairs of CAR-T cell therapy.
Insights
This study analyzed over 1200 CAR-T clinical trials to identify novel dual-target pairs. Five promising new pairs, including CD19/CD7, were discovered for advanced CAR-T cell therapy development.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptor (CAR)-T therapy has seen rapid growth since 2017, with over 100 new clinical trials annually.
- 1649 clinical studies have explored CAR-T targets and target pairs, necessitating advanced analytical methods for discovery.
Purpose of the Study:
- To employ a data-driven approach using clinical trial data to identify novel dual-target pairs for CAR-T cell therapy.
- To provide a reference for researchers and developers in selecting new CAR-T targets.
Main Methods:
- Screened 1283 non-withdrawal interventional CAR-T clinical trials from clinicaltrials.gov, covering 96 targets and 74 target pairs.
- Utilized Circos plots and temporal network plots for visualizing target-indication relationships.
- Inferred and validated new target pairs based on shared indications, expression patterns, literature, and patent information.
Main Results:
- Identified five novel dual-target pairs for CAR-T therapy, including CD19/CD7, CD19/CD5, CD19/CD37, and CD19/BAFFR.
- Validated these target pairs through expression patterns, scientific literature, and patent analysis.
- Demonstrated the utility of clinical trial data in uncovering potential CAR-T targets.
Conclusions:
- This study offers new insights into CAR-T target profiling by analyzing clinical trial data.
- The identified dual-target pairs provide a foundation for future CAR-T cell therapy research and development.
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