Enhancing Immunotherapy of Neuroblastoma
Patients diagnosed with "high risk" neuroblastoma have a high rate of failure (death) even after aggressive drug treatment and bone marrow transplantation leaves most children "cured". In 2010, we reported on the efficacy of an antibody therapeutic ch14.18, which reduces disease recurrence to about 25%. In 2015, after a long clinical trial, ch14.18 (renamed dinutuximab) received FDA approval and is now available to treat children. Alas, while fewer children are dying, even one death from this disease is too many, never mind 25%!
In view of the favorable effect dinutuximab has on survival, it is only logical that any advances in neuroblastoma therapeutics should build upon this success. However, dinutuximab has strong side effects that prevent us from simply increasing the amount of drug a child can be given, requiring us to think creatively about combining dinutuximab with other drugs. On this point, DFMO was tested many years ago as an anti-cancer agent but failed to decrease deaths from active cancer. However, new research in colon cancer has shown this drug may have promise in preventing disease recurrence when given to patients in remission. DFMO may also make the body's immune system stronger. Dinutuximab is approved to prevent neuroblastoma recurrence and works by using the patient's immune system.
In this proposal, we hypothesize that DFMO will improve dinutuximab effectiveness when the two drugs are used together. Furthermore, as both agents are FDA approved, a successful result in this study could transition to clinical trials in patients relatively easily.