Australian Scientists Develop Promising Therapy for Deadly Childhood Cancers

Sydney: Researchers at the University of Queensland (UQ) have developed a groundbreaking treatment for pediatric sarcomas using engineered immune cells, offering hope for young patients battling the aggressive disease.

Published in Clinical and Translational Medicine, a groundbreaking study introduces a novel immunotherapy approach using engineered natural killer (NK) cells to target pediatric sarcomas, a group of aggressive cancers that significantly contribute to childhood cancer-related deaths.

Pediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma, are among the most challenging malignancies to treat, with survival rates for advanced stages remaining stagnant at approximately 20% over the past three decades. Despite advances in oncology, effective therapies for these tumors remain limited, necessitating urgent innovation in treatment strategies.

Researchers have developed a chimeric antigen receptor (CAR)-modified NK cell therapy aimed at targeting the ephrin type-A receptor-2 (EphA2), a protein overexpressed in multiple pediatric sarcomas. This approach builds on the limitations of CAR-T cell therapy, which has struggled to demonstrate efficacy in solid tumors due to issues such as poor tumor infiltration, immunosuppressive microenvironments, and toxicity risks. Unlike CAR-T cells, CAR-NK cells offer enhanced tumor targeting, reduced off-target effects, and improved safety, making them an attractive alternative for treating pediatric sarcomas.

The study demonstrated the successful expression of the EphA2-targeted CAR on NK cells following electroporation, confirming the feasibility of genetic modification through transient messenger RNA (mRNA) transfection. Unlike traditional viral transduction methods, mRNA-based engineering provides a safer, non-integrative approach, minimizing long-term genetic risks.

Researchers further optimized the process by introducing chemical modifications to enhance mRNA stability, prolonging EphA2-CAR protein expression and increasing the functional lifespan of the modified NK cells.

In preclinical trials, EphA2-targeted CAR-NK cells exhibited potent cytotoxic activity against sarcoma cell lines in vitro, including rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. More significantly, in vivo studies using rhabdomyosarcoma and osteosarcoma mouse models revealed strong anti-tumor responses, demonstrating the potential of this therapy to effectively target and eliminate cancerous cells. These findings mark a substantial advancement in the development of safer and more effective immunotherapies for pediatric sarcomas.

The significance of this research extends beyond pediatric sarcomas, as the use of CAR-NK cells could be applied to other hard-to-treat malignancies, including triple-negative breast cancer and other solid tumors. The study underscores the importance of exploring new immunotherapy strategies that harness the body’s own immune system to fight cancer, particularly for pediatric patients who face limited treatment options. By overcoming the barriers faced by CAR-T cells in solid tumors, this innovative approach opens new possibilities for improving cancer treatment outcomes.

The researchers emphasize that further studies are needed to optimize this therapy, including clinical trials to evaluate safety and efficacy in human patients. Future directions include combining EphA2-CAR NK cells with immune checkpoint inhibitors or other immunomodulatory agents to enhance their effectiveness. Additionally, more advanced preclinical models that mimic the complexity of human tumor microenvironments could help refine therapeutic strategies and accelerate clinical translation.

With pediatric sarcomas remaining among the most difficult cancers to treat, this study represents a major breakthrough in the search for effective immunotherapies. By leveraging NK cell technology, the research lays the foundation for developing next-generation treatments that could significantly improve survival rates and quality of life for young cancer patients. Scientists remain optimistic that this approach could redefine pediatric oncology and provide renewed hope for children and families affected by these aggressive cancers.