'ALIEN GENE TRANSFECTION IN THE THERAPY OF METASTASES'

这些研究的目标是开发和使用基因 用于治疗已建立的转移的工程化鼠肿瘤细胞。 这些研究的基本原理是基于肿瘤细胞 表达“半抗原样”抗原，其免疫原性差，但仍保留 抗原性，因为它们可以被产生的免疫应答识别。 转染和表达强病毒抗原，如 血凝素（HA）提供了“联想识别”的基础，其中 对HA的应答促进对肿瘤相关抗原（TAA）的应答。 这一点已经用三种不同的小鼠肿瘤得到了证明， 用HA转染并表达HA，可以保护免受非HA的攻击。 转染的亲本细胞。 这些研究的第二个目标是 具有编码淋巴因子如IL-2和IL-4的基因的鼠肿瘤，或 IFN-γ。 这些新的细胞系将使我们能够解决的作用， 迟发型超敏反应（65 kDa）和MHC I类表达（IFN-γ） γ），在肿瘤排斥中。 它们也将使我们能够确定更多 结论是，如果绕过T细胞帮助加速免疫反应（IL- 4）。 我们的最终目标是利用这些基因工程细胞， 本发明提供了用于治疗小鼠中已建立的转移的药物组合物。

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.