In a significant advancement in cancer research, scientists from St. Jude Children's Research Hospital have made remarkable strides in chimeric antigen receptor (CAR) T-cell immunotherapy for acute myeloid leukemia (AML). The researchers focused on overcoming the common issues associated with CAR T cells, such as immune escape and therapy efficacy. By integrating a small peptide and using the computational approach, they improved the therapy's ability to seek and eliminate cancer cells. The study demonstrated the effectiveness of a unique dual-targeted CAR design, which outperformed single-targeted CARs in both in vitro and in vivo experiments. The research also utilized AI-based structure prediction tools to identify the most effective linker configuration for CAR design, offering valuable insights for future improvements in leukemia and other malignancies.
Improving CAR T Cell Immunotherapies
According to St. Jude's official release, scientists have improved bispecific chimeric antigen receptor (CAR) T cell immunotherapies for AML using computational analysis. They devised an additional means for the therapy to locate and eradicate cancer cells with the aid of a small peptide. This approach can be extrapolated to other tumors and shows promise in enhancing CAR T cell function. The team used computational structure predictions and compared structures with experimental results to find that shorter, more flexible linkers would work better in their models.
Computational Approach and AI in Cancer Research
St. Jude's researchers also showcased how a computational approach integrating AlphaFold predicted protein models could aid in understanding the impact of structure on antigen recognition and therapy efficacy. In an attempt to overcome the problems encountered by dual targeting approaches, the researchers added a small peptide to the CAR to act as the binder for the second targeted protein. They also employed artificial intelligence to untangle the performance of two target constructs and found that shorter, more flexible linkers would function better in their models. This study demonstrates promise for improving CAR T cell function and can be widely extrapolated to other tumors, as reported by Newswise.
St. Jude's Contributions to Pediatric Cancer Research
St. Jude Children's Research Hospital has achieved significant milestones in pediatric cancer research, including the creation of a molecular super glue to target cancer-related proteins, tracking of the HOXA9 gene for AML, and identifying two common biomarkers to predict heart risk in childhood cancer survivors. The hospital has also updated the genomic landscape for pediatric AML, enabling new treatment possibilities and developed a new antibiotic to address resistance in Mycobacterium abscessus. Additionally, St. Jude has made strides in understanding predisposition in bilateral Wilms tumor, prediabetes treatment for childhood cancer survivors, and the functional targets of oncogenic HOXA9 in high-risk pediatric leukemia. Furthermore, the hospital has identified a promising target for CAR T-cell therapy in brain and solid tumors.
St. Jude's Commitment to Innovation
St. Jude Children's Research Hospital continues to be at the forefront of innovation, with its recent appointment of Sara Federico MD as the director of the Solid Tumor Division. Federico is a recognized clinician researcher focusing on novel treatments and clinical trials for difficult-to-treat childhood cancers, such as high-risk neuroblastoma and relapsed sarcomas. She is currently leading five clinical trials, including two pioneering new approaches to treat neuroblastoma. This appointment exemplifies St. Judeâs commitment to leading the way in understanding, treating, and curing childhood cancer as the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children.