HUNTER JONUS, PHD
Emory University School of Medicine
CureSearch Young Investigator Award: 2024-2026
Focus: Pediatric neuroblastoma
Project title: Driving tumor infiltration and persistence of gd T cell therapies for NB
Neuroblastoma, the most common extracranial solid tumor in children, presents a formidable challenge in pediatric oncology. Approximately half of neuroblastoma patients are diagnosed with high-risk disease, which has an especially aggressive 50% survival rate, illustrating that the urgency for innovative treatment approaches is paramount.
Dr. Jonus is leading groundbreaking research in combating this aggressive disease. Her team's research focuses on developing novel treatment options for patients suffering from high-risk neuroblastoma utilizing cellular immunotherapy. Her innovative approach incorporates a unique T cell subset known as gamma delta (γδ) T cells, which can be isolated from healthy donors, expanded ex vivo, and infused into patients to target and eliminate tumors, including neuroblastoma.
Dr. Jonus seeks to enhance the effectiveness of γδ T cell therapy by engineering these cells to better recognize and infiltrate solid tumors while extending their longevity within the body. By incorporating chimeric antigen receptors and cytokine secretion pathways, Dr. Jonus aims to optimize γδ T cell function and bolster their anti-tumor activity.
Research Update December 2024:
Over the past 6 months, Dr. Jonus and her team have made significant progress in developing PTK7 CAR γδ T cells for the treatment of neuroblastoma. They have successfully generated these CAR T cells and tested their efficacy and ability to traffic to the tumor site in vitro. Despite unexpected challenges in CAR expression, they have overcome these hurdles and are continuing to test their effectiveness with or without secretion of IL-15, a cytokine known to enhance T cell survival and activity. Additionally, they have established the infrastructure to produce the necessary components for these studies in-house, reducing the reliance on commercial suppliers and paving the way for faster, more cost-effective research. Furthermore, the team has explored how to effectively combine γδ T cell therapy with immune checkpoint blockade (ICB). To this end, they have identified TIGIT and TIM-3, inhibitory receptors that can limit T cell function, as key factors influencing γδ T cell activity. The team is now performing in vitro testing to enhance the effectiveness of this approach by combining γδ T cell treatment with anti-TIGIT ICB to block these inhibitory signals.
"High-risk neuroblastoma poses significant challenges in pediatric oncology, with survival rates plummeting below 20% upon relapse after chemotherapy," explains Dr. Jonus. "My research aims to revolutionize treatment paradigms by harnessing the potential of γδ T cell immunotherapy to provide safer and more effective options for patients facing this aggressive disease."
- Dr. Hunter Jonus