VACCINE THERAPY OF PEDIATRIC MALIGNANCIES UTILIZING DENDRITIC CELLS

这项研究是在第1571号议定书之前批准的试点研究。人类癌症的免疫治疗在很大程度上被限制在黑色素瘤和肾癌的应用上，这两种肿瘤是免疫原性较弱的肿瘤，而两种肿瘤主要局限于成年人。儿童癌症在制定疫苗策略时通常被忽视，尽管其中一些恶性肿瘤具有免疫原性，尽管儿童在许多病理状态下表现出增强的免疫反应。我们建议在神经母细胞瘤、软组织肉瘤、骨尤文氏肉瘤和Wilm肿瘤患者中研究新的疫苗策略，这些患者代表令人烦恼的肿瘤实体，但有大量关于细胞表面抗原表达的数据。疫苗的成分将利用迅速发展的关于树突状细胞(DC)生物学的知识和技术。树突状细胞是一种强大的抗原提呈细胞，在体外可以被抗原冲击，然后用来刺激初始T细胞的初级免疫反应。在临床前研究中，DC被证明在对免疫原性差的肿瘤产生特异性免疫反应导致肿瘤消退方面非常有效。这些临床前研究为儿童晚期癌症患者DC的研究提供了理论基础。将从患者的外周血中分离出DC，并将其与自体肿瘤冲击以产生疫苗试剂。建议的临床研究将在FDA批准的IND(BB-IND#6958 to Dr.Mule，已获得允许治疗儿童的修订IND)下进行。

This study was the approved pilot study that preceded Protocol # 1571. 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.)