Predicting Outcome and Ameliorating Toxicities of the Immunotherapy of Neuroblastoma

Until last year, the majority of patients diagnosed with high risk neuroblastoma succumbed to the disease despite intensive chemotherapy and bone marrow transplantation. In 2010, the PI of this proposal reported a major improvement in survival from 46% to 66% using an antibody therapeutic. Unfortunately, we cannot predict who will respond to this treatment which is frequently accompanied by serious side effects.

In this proposal, we will search for biological markers that may predict patient outcome and side effects. Antibody therapeutics work by attaching to and killing cancer cells. We predict that patients whose cells can attach to the antibody most tightly are the ones most likely to respond to the therapy. We will determine the importance of attachment strength by analyzing DNA variations involved in antibody binding and correlate this with patient survival. We believe this will allow us to predict patient response and identify patients who may benefit from alternative therapies that may give them better chance of survival. Treatment side effects can dramatically influence quality of life. Antibody therapeutics are made in animal cells, which can modify the antibody without affecting its ability to kill the cancer cells. We will determine in this study whether some patients are having a reaction to these modifications. If correct, it is possible to modify the conditions under which the antibody is made to eliminate these modifications and minimize side effects while retaining the beneficial effects of the antibody.