The role of immunogenetics in natural killer cell targeting of neuroblastoma
Neuroblastoma is the most frequently diagnosed cancer in infancy, comprises more than 7% of cancers in patients younger than 15 years of age, and is responsible for 15% of all childhood cancer deaths. There remains a need for novel treatment strategies to eliminate residual disease resistant to current therapies. We will study if natural killer (NK) cells, an important cell in our immune system, and the immune genes responsible for their behavior play a role in the control and eradication of neuroblastoma. We have previously shown that NK cells and the immune genes that control them are important in eliminating cancers such as acute leukemia, particularly leukemias that have been treated by bone marrow transplants. Because very aggressive neuroblastoma tumors can also be treated by bone marrow transplants, we propose that examination of the NK immune genes in neuroblastoma patients may be useful in predicting which patients will have better outcomes. Our preliminary data supports this hypothesis, and we propose to perform the biological studies to investigate how these NK cells behave in neuroblastoma patients. As a result of similar genetic and NK function studies, treatment options for acute leukemia now include the infusion of NK cells, which have been carefully chosen based on the immune genes of the patient and the NK donor. We anticipate that the results from our proposed genetic and NK function studies will support our plans for the development of a novel treatment for neuroblastoma using NK cells.