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.

PubMed

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.