'ALIEN GENE TRANSFECTION IN THE THERAPY OF METASTASES'

这些研究的目标是开发和利用基因 用于治疗已确定的转移的工程化小鼠肿瘤细胞。 这些研究的基本原理是基于一种假设，即肿瘤细胞 表达免疫原性较差但仍存在的“半抗原样”抗原 抗原性，因为它们可以被产生的免疫反应识别。 一种强病毒抗原的转染和表达，如 血凝素(HA)为“联想识别”提供了基础，其中 对HA的应答促进了对肿瘤相关抗原(TAA)的应答。 这一点已经在三种不同的小鼠肿瘤上得到了证实，当 转基因并表达HA，可抵御非 转染亲本细胞。这些研究的第二个目标是将 携带IL_2和IL-4等淋巴因子编码基因的小鼠肿瘤，或 干扰素-γ。这些新的细胞系将使我们能够解决 迟发型超敏反应(65 KDa)与MHC-I类分子表达 伽玛)，在肿瘤排斥反应中。它们还将使我们能够确定更多 结论是，如果绕过T细胞有助于加速免疫反应(IL- 4)。 我们的最终目标是使用这些基因工程细胞，或者 它们的组合，用于治疗已建立的小鼠转移瘤。

The goal of these investigations is to develop and use genetically engineered murine tumor cells for the treatment of established metastases. The rationale for these studies is based on the hypothesis that tumor cells express "hapten-like" antigens that are poorly immunogenic but remain antigenic in that they can be recognized by an engendered immune response. The transfection and expression of a strong viral antigen such as hemagglutinin (HA) provides a basis for "associative recognition", where a response to HA fosters a response to the tumor associated antigen (TAA). This point has been proven using three different murine tumors which when transfected with, and expressing HA, protect against a challenge with non- transfected parent cells. A second goal of these studies is to transfect murine tumors with genes coding for lymphokines such as IL_2 and IL-4, or IFN-gamma. These new cell lines will allow us to address the role of delayed type hypersensitivity (65kDa) and MHC Class I expression (IFN- gamma), in tumor rejection. They will also allow us to determine more conclusively if bypassing T-cell help accelerates the immune response (IL- 4). Our ultimate goal is to use these genetically engineered cells, or combinations thereof, to treat established metastases in mice.