Targeted Nanoparticles for Genetic Engineering of Human Natural Killer Cells for Neuroblastoma Therapy

Dr. Ketan Ghaghada, Ph.D. – Baylor College of Medicine, Houston TX

Neuroblastoma (NB) is the most common solid tumor in children below 5 years of age. It is a devastating illness for children with advanced disease. Survival rates are only around 40%. Those children that do survive suffer life-long medical problems. Immunotherapy, which trains the body’s own immune cells to specifically recognize and kill tumors, offers potential for a less toxic and long-lasting cure for children with NB. However, current methods to train immune cells require removing the cells from the body, modifying them in the lab, and then administering the trained immune cells back to the patient. This process takes a long time, costs a lot, and sometimes results in immune cells that don’t work very well, making it hard for many children to benefit from immunotherapy. To address these big problems, we have developed a nanotechnology called lipid nanoparticles (LNPs) that can deliver gene editing payload for training immune cells directly within the body. In this work, we will test the ability of LNPs to effectively train immune cells to kill NB. We will first optimize the way LNPs are made to maximize training of immune cells. Then, we will test how well the LNP-trained immune cells kill tumors in mice with NB tumors. Our LNP technology has the potential to improve how well immune cells kill NB. Also, LNPs would train immune cells more efficiently. This would reduce costs and improve patient experience, increasing access to life saving immunotherapy for many children.