The challenge of targeting cancer therapy to affect cancer cells without harming healthy cells has been a significant issue in the field of chimeric antigen receptor (CAR) T-cell therapy. Researchers at St. Jude Children’s Research Hospital have identified 156 potential targets for CAR T-cell therapy through a comprehensive analysis paired with experimental validation in vivo. The findings, published in Nature Communications, offer hope for the development of curative approaches in cancer immunotherapy.
One of the targets identified by the researchers, COL11A1, has shown promise in mouse models. Other targets, such as anti-fibronectin CAR T cells, have also shown potential in cell lines. Most of the targets identified have yet to be tested, but they are publicly available for other researchers to explore and pursue in their own studies. This comprehensive list of targets provides a valuable resource for the scientific community in the pursuit of effective cancer immunotherapy.
The researchers have made their data available through a web portal called SCE-Miner, which is freely accessible on the St. Jude Cloud platform. This portal allows external researchers to access the data and utilize the internal analysis tools to further their own research. By providing this resource to the scientific community, the researchers hope to empower others to explore and evaluate the identified targets for potential therapeutic applications.
The St. Jude method of identifying CAR T-cell targets differs from previous approaches in several key ways. The researchers analyzed a larger sample size of pediatric tumor samples across all major cancer types, expanding the candidate pool for potential targets. In addition to focusing on membrane-associated proteins, the researchers also considered proteins in the extracellular matrix, which led to the identification of novel targets for CAR T-cell therapy.
By examining exons and isoforms of genes in cancer cells, the researchers were able to identify cancer-specific targets that could be potentially targeted by CAR T cells. Alternative splicing of exons in cancer cells creates isoforms that differ from normal cells, providing unique targets for immunotherapy. The robust analysis approach used by the researchers allowed for the evaluation of cancer-specificity at both the isoform and gene level, providing valuable insights into potential targets for CAR T-cell therapy.
