MOLECULAR PROFILE OF MELANOMA AND NEUROBLASTOMA ANTIGENS

这项提议的目的是对肿瘤进行深入的研究 恶性黑色素瘤和恶性黑色素瘤两种肿瘤系统的侵袭转移 神经母细胞瘤。这将通过两个主要途径来实现：第一， 通过对生物的复杂过程有一个基本的了解 和分子水平，最好使用至少五种不同的抗原 在这些肿瘤上表达，并已被确立为有效 特异性单抗介导的肿瘤杀伤靶点。 二是先优化，再结合个别化处理 采取协同行动销毁人类肿瘤和 它们在实验动物模型系统中的中转酶。这些影响将 结合对宿主免疫系统的操纵和靶向 化疗药物、放射性核素、分化剂和核糖体 靶向有效的单抗灭活蛋白(RIP) 肿瘤抗原靶标。 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抗识别抗原 已经被建立为有效目标的细胞 近五年来单抗介导的肿瘤杀伤 这个实验室的工作成果。使这些系统达到最佳效率 将使用各种方法进一步了解肿瘤侵袭的基本知识。 和转移。其他实验系统将用试剂进行优化 和治疗模块结合在一起，以在 破坏人类黑色素瘤和神经母细胞瘤转移。它是 预期这里所述目标的实现将导致 更好地了解肿瘤生物学，并有望提供新的和 治疗人类癌症的有效方法。

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.