REGRESSION OF EXPERIMENTAL BURKITT'S LYMPHOMA IN ATHYMIC MICE

施用用特异性抗体转导的淋巴细胞或肿瘤细胞 细胞因子基因代表了治疗癌症的新方法。 通过 或者提供抗肿瘤效应细胞或者刺激抗肿瘤效应细胞， 这些实验方式导致了肿瘤部位的免疫力， 在一些肿瘤中，致瘤性降低，现有肿瘤消退， 实验模型 最近，逆转录病毒介导的体内转移的a 疱疹病毒源性胸苷激酶（tk）基因进入大脑的比例 神经胶质瘤肿瘤细胞使它们对抗病毒药物的破坏敏感 药 它还导致其他肿瘤细胞的死亡，而不是转导的。 tk基因，通过一个不明确的旁观者效应。 尽管有这些 实验结果表明，靶向效应淋巴细胞以及 抗癌细胞因子和特定肿瘤的药物敏感因子 临床应用有限，因为它涉及相对 复杂的程序没有广泛提供。 当皮下注射到辐射的无胸腺（裸）小鼠时，人B 用EB病毒（EBV）永生化的细胞不能生长， 产生小肿瘤，很快通过坏死和疤痕消退。 这种退化的机制尚未完全理解，但已经 这是由于残留的宿主免疫力。 在同一实验系统中， 人伯基特淋巴瘤细胞通常发展成致命恶性 肿瘤的 在本研究中，我们检查了是否接种EB病毒永生化， B细胞可能对实验性伯基特氏病有抗肿瘤作用 无胸腺小鼠的淋巴瘤。 同时接种EBV永生化B 细胞和伯基特淋巴瘤细胞在同一皮下部位， 肿瘤随着坏死和疤痕的形成而消退。 同样地， 同时接种EBV-永生化B细胞和Burkitt's 淋巴瘤细胞在不同的皮下部位导致退化， 伯基特氏肿瘤的比例 此外，大多数现有的 人伯基特肿瘤在治疗后随着坏死和瘢痕形成而消退， 瘤内接种EBV永生化B细胞。 EB病毒- 永生化B细胞继续发挥这种抗肿瘤作用，即使当 用辐射杀死。 Burkitt淋巴瘤的实验研究 这里描述的治疗利用了无胸腺小鼠的排斥能力， EBV-永生化B细胞靶向有效的抗肿瘤反应， 恶性细胞通常不能诱发它。

Administration of lymphocytes or tumor cells transduced with specific cytokine genes represent novel approaches for the treatment of cancer. By either providing antitumor effector cells or stimulating antitumor immunity at the tumor site these experimental modalities have resulted in decreased tumorigenicity and regression of existing tumors in a number of experimental models. Recently, retroviral-mediated transfer in vivo of a herpes-virus-derived thymidine kinase (tk) gene into a proportion of brain glioma tumor cells rendered them sensitive to destruction by an antiviral drug. It also led to death of other tumor cells, not transduced with the tk gene, through a poorly defined bystander effect. In spite of these experimental results, the targeting of effector lymphocytes as well as anticancer cytokines and drug sensitivity factors to particular tumor sites has had limited clinical applications because it involves relatively complex procedures not widely available. When injected subcutaneously into irradiated athymic (nude) mice, human B cells immortalized with Epstein-Barr virus (EBV) either fail to grow or give rise to small tumors that soon regress through necrosis and scarring. The mechanism for this regression is not fully understood but has been attributed to residual host immunity. In the same experimental system, human Burkitt's lymphoma cells generally develop into lethal malignant tumors. In the present study, we examined whether inoculation of EBV-immortalized B cells might have an antitumor effect against experimental Burkitt's lymphoma in athymic mice. Simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in the same subcutaneous site resulted in tumors that regressed with necrosis and scarring. Similarly, simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in separate subcutaneous sites resulted in regression of a proportion of the Burkitt's tumors. Furthermore, most of the established human Burkitt's tumors regressed with necrosis and scarring after intratumor inoculations with EBV-immortalized B cells. The EBV- immortalized B cells continued to exert this antitumor effect even when killed with irradiation. The experimental approach to Burkitt's lymphoma treatment described here exploits the ability of athymic mice to reject EBV-immortalized B cells to target an effective antitumor response to malignant cells normally incapable of eliciting it.