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基因修饰的肿瘤细胞所分泌的TNF(肿瘤坏死因子)能够主要通过诱导机体的抗肿瘤免疫反应而使机体产生强大的抗肿瘤免疫功能,这一效应的发挥需要肿瘤局部TNF的持续的存在并具有剂量依赖性,同时不应伴有全身性毒副作用.在体内,分泌TNF的肿瘤细胞局部浸润的细胞主要是巨噬细胞及CD4~+和CD8~+T淋巴细胞,由于在有效的抗肿瘤免疫反应中必需巨噬细胞及CD8~+T细胞的参与,CD4~+T细胞似为无辜旁观者细胞.肿瘤细胞所分泌的TNF在T细胞缺陷鼠中也有一定作用,但大多数资料表明T细胞对于肿瘤细胞的完全清除是必需的.根据所选择的肿瘤细胞类型及转染细胞所分泌的TNF水平,TNF所引起的实验动物全身性毒副作用包括恶液质及消瘦、部分体内实验结果表明,TNF基因转染的肿瘤细胞不仅不能抑制肿瘤细胞的生长,反而会促进肿瘤的转移.将TNF基因转染的肿瘤细胞制备的瘤苗也不能使机体对亲本肿瘤的侵袭产生保护性免疫反应.
The TNF (tumor necrosis factor) secreted by genetically modified tumor cells can cause the body to produce powerful anti-tumor immune functions mainly by inducing anti-tumor immune responses of the body. This effect requires the sustained existence of tumor local TNF and has It is dose-dependent and should not be accompanied by systemic side effects. In vivo, the cells that infiltrate TNF-secreting tumor cells are mainly macrophages and CD4~+ and CD8~+ T lymphocytes due to effective anti-tumor immunity. In the reaction, macrophages and CD8~+ T cells were required to participate, and CD4~+ T cells appeared to be innocent bystander cells. Tumor cells secreted TNF also have a role in T cell deficient mice, but most data indicate that T cells Complete removal of tumor cells is necessary. Depending on the type of tumor cells selected and the level of TNF secreted by the transfected cells, the systemic side effects of TNF-induced experimental animals include dyscrasia and wasting, and some in vivo experiments show that The tumor cells transfected with TNF gene can not only inhibit the growth of tumor cells, but also promote tumor metastasis. The tumor vaccines prepared from tumor cells transfected with TNF gene are not Enables the body to produce a protective immune response to the invasion of the parental tumor.