William E. Janssen, Ph.D. Shari Pilon-Thomas, Ph.D. James J. Mule, Ph.D

Funded by the Dick Vitale Gala

Neuroblastoma is an aggressive cancer of the nervous system that primarily affects very young children. Half of the children affected by this disease are less than 18 months old. Neuroblastoma represents 8-10% of all childhood cancer cases, but 15% of all childhood cancer deaths, and over the past twenty years, the survival statistics have not improved, with only 40% of all affected children expected to have any hope of a long-term survival. Treatments for neuroblastoma are generally aggressive, and include multiple treatment types including surgery, radiation, chemotherapy, and hematopoietic progenitor cell (HPC) transplant (more often referred to as bone marrow transplant). It is this latter treatment type, HPC transplant, that was associated with the greatest improvement in survival when it was introduced for neuroblastoma treatment over 20 years ago, and which forms the foundation for this proposal. In treating neuroblastoma, the actual transplant is preceded by a regimen of very high dose chemo- and radiation-therapy. This reduces the patient’s tumor burden to the lowest possible level, but also wipes out the blood forming cells of the bone marrow. The HPC that are transplanted re-establish healthy bone marrow. In the process of marrow re-establishment, the patient’s immune system also re-establishes. It has been seen in animal models and in some clinical situations that a specific type of cells in the immune system, called lymphocytes, will preferentially recognize and respond to the agents in vaccines if those vaccines are administered early during this re-establishment process. Our goal in the proposed study will be to create vaccines from killed neuroblastoma cells taken from each patient, and then to administer those vaccines during recovery from HPC transplant. We will follow all patients in this study for an entire year to determine if this vaccine protocol produces immunity against the patient’s own neuroblastoma cells, and also if it results in tumor suppression. Autologous HPC transplant has been used in the treatment of neuroblastoma for over twenty years, but the success of this therapy has remained below 40 percent. Dendritic cell therapy has been tested in a very limited number of patients with some hint of promise. This study will be the first effort to combine these two approaches in a way that we expect to be synergistic. This unique study is being carried out as a collaborative effort between the Cell Therapies Facility of the Moffitt Cancer Center and the Blood and Marrow Transplant Unit of All Children’s Hospital.

 

Location: H. Lee Moffitt Cancer Center and Research Institute - Florida
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