MOLECULAR PROFILE OF MELANOMA AND NEUROBLASTOMA ANTIGENS

这项建议的目的是对肿瘤进行深入研究， 在两种人类肿瘤系统恶性黑色素瘤和 神经母细胞瘤 这将通过两个主要途径来实现：第一， 通过对生物学中复杂过程的基本了解， 和分子水平，优选使用至少五种不同的抗原 在这些肿瘤上表达，并且已经被确定为有效的 特异性单克隆抗体介导的肿瘤破坏靶点。 第二，通过先优化再结合个体化治疗 在破坏人类肿瘤中协同作用的方式， 它们在实验动物模型系统中的转移酶。 这些效果将 联合收割机操纵宿主的免疫系统， 化疗药物、放射性核素、分化剂和核糖体 通过单克隆抗体灭活蛋白（RIP）， 肿瘤抗原靶点。 这项研究建议的基本原理是利用 人黑色素瘤和神经母细胞瘤的单克隆抗体确定的抗原 已经被确立为有效靶点的细胞， 单克隆抗体介导的肿瘤破坏 这个实验室的努力。 使这些系统达到最佳效果 这些方法将用于进一步获得肿瘤侵袭的基础知识 和转移。 其他实验系统将与试剂优化 和治疗模块组合以在治疗中最协同地起作用， 破坏人黑色素瘤和神经母细胞瘤转移。 是 预计实现这里概述的目标将导致 更好地了解肿瘤生物学，并希望提供新的， 治疗人类癌症的有效方式。

The objective of this proposal is to conduct indepth studies of tumor invasion and metastasis in two human tumor systems, malignant melanoma and neuroblastoma. This will be accomplished by two major approaches: First, by gaining a basic understanding of the complex processes at the biological and molecular levels, using at least five different antigens preferentually expressed on these neoplasms and already will established as effective targets for tumor destruction mediated by specific monoclonal antibodies. Second, by first optimizing and them combining individual treatment modalities to act synergistically in the destruction of human tumors and their mestastases in experimental animal model systems. These effects will combine manipulations of the host's immune system with targeting of chemotherapeutic drugs, radionuclides, differentiation agents and ribosome inactivating proteins (RIP) by monoclonal antibodies directed to effective tumor antigen targets. The basic rationale underlying this research proposal is to make use of monoclonal antibody-defined antigens on human melanoma and neuroblastoma cells that have already been established as effective targets for monoclonal antibody-mediated tumor destruction during the last five years of this laboratory's efforts. To render these systems optimally effective approaches will be used to gain further basic knowledge of tumor invasion and metastasis. Other experimental systems will be optimized with reagents and treatment modulities being combined to act most synergystically in the destruction of human melanoma and neuroblastoma metastases. It is anticipated that achievement of the objectives outlined here will result in a better understanding of tumor biology and hopefully provide new and effective modalities for the treatment of human cancer.