VACCINE THERAPY OF PEDIATRIC MALIGNANCIES UTILIZING DENDRITIC CELLS

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Immunotherapy of human cancers has largely been restricted to applications in melanoma and renal cell cancer, two tumors that are largely confined to the adult population. Pediatric cancers have been generally neglected when developing vaccine strategies, despite the potential importance of the immune system in some of these malignancies and despite the enhanced responsiveness of the immune system demonstrated by children in many pathologic states. We propose to investigate new vaccine strategies in patients with neuroblastoma, soft tissue sarcomas, Ewings sarcomas of bone, and Wilms tumors which represent difficult pediatric tumors, and yet for which considerable information about cell surface antigen (tumor proteins which can be recognized by the immune system) expression exist. The composition of the vaccines will take advantage of rapidly developing knowledge and technology regarding the biology of dendritic cells (DC). DC are potent antigen-presenting cells which can be pulsed with antigens in culture and subsequently used to stimulate primary immune responses in T cells. In laboratory studies and early clinical studies, DC have been shown to be highly effective at generating specific immune responses to tumors leading to tumor regression. These studies serve as rationale for the study of DC in pediatric patients with advanced cancer. DC will be generated from the patient+s peripheral blood and pulsed with autologous (the patient's own) tumor to generate vaccine reagents. In addition, one half of the immune cells will be exposed Keyhole Limpet Hemocyanin (KLH). KLH is a substance which stimulates an immune response and which will be used as a control to verify whether the immunization technique has worked. During and after the series of immunizations, blood tests, skin tests, x-rays, and scans will be done to assess the patients response to the immunizations (tumor shrinkage, increase in reactive T-cells, etc.), and to monitor for side effects.