Regression of established murine adenocarcinoma by in vivo allogeneic MHC gene transfer using electroporation and modification of donor MHC antigens by antisense gene transfer to prevent rejection of transplanted organs

1.在我们的第一项研究中，我们研究了低抗原大鼠腺癌细胞在转染后与一个类似物类I主要历史兼容性复合体（MHC）基因体外，并研究了在直接的类似物MHC基因转移到可用于确定的肿瘤中使用体内电发射可能会刺激宿主免疫反应，并提供一种免疫疗法效果。Mammary adenocarcinoma cells （MAT B III） originated from F344rat（RT1A-D11-D1） were transfected with a plasmid DNA encoding RT1A-D1 （pcMRT1A） in vitro。RT1A的expression of RT1A的D1a的antigen on the tumor cells result in stimulating cytolytic T-cell res\against specific gene products。Furthermore，我们研究了直接同源性MHC类I基因转移到肿瘤生长在合成宿主体内的体内。pcMRT 1A-脂氧蛋白复合体的内部注入，由八个电脉冲（99微秒，400 V/cm）通过两个电 ... More 在肿瘤的每一个方面都被发现有标记的回归在肿瘤的生长和延长的生存周期中。这些结果表明，转移相似类I MHC基因直接进入肿瘤中使用体内电泳可能会产生细胞介导的免疫反应并提供一种免疫治疗效应对稳定的肿瘤. 2。在我们的第二项研究中，我们研究了一个反义向量的插入，该插入可以向下调节目标抗原的表达，并防止移植器官的拒绝。体外研究，对捐赠者MHC类I抗原表达的向下调节在捐赠者细胞上被观察到，在转移等离子体载体后，将捐赠者目标抗原的免疫反应转移到体外，也是免疫反应。在体内，有效地将反义DNA转移到捐赠者移植器官的器官上是非常困难的。现在，我们正在开发新的技术，以提供有效的体内转染。Less（低）

1. In our first study, we investigated immunogenicity of low-antigenic rat adenocarcinoma cells after transfection with an allogeneic class I major histocompatibility complex (MHC) gene in vitro, and studied whether direct allogeneic MHC gene transfer into the established tumor using in vivo electroporation might stimulate the host immune response, and also provide an immunotherapeutic effect. Mammary adenocarcinoma cells (MAT B III) originated from F344 rat (RT1AィイD11ィエD1) were transfected with a plasmid DNA encoding RT1AィイD1aィエD1 (pcMRT1A) in vitro. The expression of RT1AィイD1aィエD1 antigen on the tumor cells resulted in stimulating cytolytic T-cell response against specific gene products. Furthermore, we investigated the antitumor effects of direct allogeneic MHC class I gene transfer into the tumor grown in the syngeneic host using in vivo electroporation. Intratumoral injection of the pcMRT1A-Lipofectin complex followed by eight electrical pulses (99μsec, 400V/cm) through two electr … More odes located on each side of the tumor induced a marked regression in tumor growth and prolonged survival periods of the host. These results indicate that transferring allogeneic class I MHC gene directly into tumor using in vivo electroporation could induce a cell-mediated immune response and provide an immunotherapeutic effect for the established tumor.2. In our second study, we examined whether insertion of an antisense vector into the allograft could down-regulate the expression of the target antigens and to prevent the rejection of transplanted organs. In vitro study, down-regulation of donor MHC class I antigen expression on the donor cells was observed after transfection of plasmid vector containing antisense of donor target antigen in vitro and also immunological response to these cells. However, in vivo, efficient transfection of antisense DNA to the donor graft organ was very difficult at present. Now we are developing new technology to provide for efficient in vivo transfection. Less