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 weakly immunogenic tumors and two that are largely confined to the adult population. Pediatric cancers have been generally neglected when developing vaccine strategies, despite the immunogenic potential of some of these malignancies and despite the enhanced immunoreactivity demonstrated by children in many pathologic states. We propose to investigate novel vaccine strategies in patients with neuroblastoma, soft tissue sarcomas, Ewing's sarcomas of bone, and Wilm's tumors which represent vexing neoplastic entities, and yet for which considerable data regarding cell surface antigen 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 vitro and subsequently used to stimulate primary immune responsed in naive T cells. In pre-clinical studies, DC have been shown to be highly effective at generating specific immune responses to poorly immunogenic-tumors leading to tumor regression. These pre-clinical studies serve as rationale for the study of DC in pediatric patients with advanced cancer. DC will be isolated from patient's peripheral blood and pulsed with autologous tumor to generate vaccine reagents. The clinical studies proposed will be conducted under an FDA-approved IND (BB-IND #6958 to Dr. Mule, an amended IND to allow the treatment of children has been obtained.)