New York Medical College Archives - Hyundai Hope On Wheels

2017

Young Investigator

Dr. Allyson Flower

Valhalla, NY

Overcoming Natural Killer (NK) Cell Resistance in Poor Risk Neuroblastoma (NB)

Neuroblastoma is one of the most common causes of cancer in childhood, and one of the leading causes of cancer related deaths. Even with highly intensive therapy, rates of resistant disease and relapse are unacceptably high. Antibody and cellular immunotherapy are mechanisms by which the body’s immune system is exploited to target cancer cells specifically, and avoid off-target effects. Natural killer cells are a component of the immune system, which act against cancer cells, especially neuroblastoma cells. However, NK cells are inadequate in number, persist transiently, and lack target specificity. Each of these mechanisms allows for tumor progression.

The purpose of this study is to develop immunotherapeutic agents to overcome each of these resistance pathways to eradicateneuroblastoma:

NK cells will be expanded in number using specialized feeder cells to enhance growth and function.
Expanded NK cells will be used to create chimeric antigen receptor modified NK cells, which are NK cells that express a receptor to specifically target the surface protein ROR1 on neuroblastoma cells.
To enhance NK cell persistence and function, IL-15 super-agonist will be combined with targeted NK cells.
A bispecific killer engager will be used to broaden NK cell targeting. The BiKE binds GD2, which is also present on the surface of neuroblastoma cells, including those that do not express ROR1. The BiKE connects NK cells to GD2 on neuroblastoma cells, leading to additional target specific tumor cell destruction.

Taken together, these novel agents strategically address each of the known immune escape mechanisms described. If successful, combined immunotherapy would be highly applicable to pediatric neuroblastoma patients in the clinical setting, and would offer a potentially more effective and less toxic therapeutic regimen, ultimately leading to improved survival.