We use human pediatric tumors as a model system to study the molecular events associated with the development of malignant tumors during childhood. Since neuroblastoma (NB) can be induced to differentiate in vitro with retinoic acid, it is a particularly useful system in which to study the molecular mechanisms regulating growth and differentiation. Our current focus is to identify additional chemicals and biologic response modifiers that control cell growth and/or induce differentiation and use recombinant DNA technology to identify the molecular mechanisms and clone the genes important for the regulation of these processes in pediatric peripheral neuroectodermal tumors. During the past year a clinical protocol utilizing trans-retinoic acid to treat children with pediatric malignancies, evolved in part from in vitro studies demonstrating its efficacy. Furthermore, t@e inclusion of interferon-gamma pretreatment of children with neuroblastoma in a TIL(tumor-infiltrating lymphocytes) therapy clinical protocol developed from in vitro studies analyzing the expression of Class I Major Histocompatibility Complex antigens on neuroblastoma tumors. Ultimately our goal is to develop new strategies and novel therapeutics based on understanding the specific alterations in these pediatric malignancies.
