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。 通过提供抗肿瘤效应细胞或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， 的实验模型。 最近，逆转录病毒介导的体内转移 疱疹病毒衍生的胸苷激酶（tk）基因的比例 脑神经胶质瘤肿瘤细胞使它们对破坏敏感 抗病毒药物 它还导致其他肿瘤细胞的死亡，而不是 通过不明确的旁观者效应，用TK基因转导。 尽管有这些实验结果，但效应物的靶向仍然是不可能的。 淋巴细胞以及抗癌细胞因子和药物敏感因子 对特定的肿瘤部位的应用有限， 它涉及相对复杂的程序，并没有广泛提供。 我们 认为肿瘤细胞的杀伤可能是由 用良性细胞接种荷瘤宿主， 如果接种到同一宿主中通常会被破坏。 我们推断 通过在体内刺激局部细胞毒性反应， 通过旁观者效应杀死肿瘤细胞。 注射时 皮下注射到辐射的无胸腺（裸）小鼠、人B细胞 用EB病毒（EBV）永生化的细胞不能生长或 形成小肿瘤，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EBV- 永生化B细胞可能对实验性的抗肿瘤作用。 无胸腺小鼠的伯基特淋巴瘤。 同时接种EBV- 永生化B细胞和伯基特淋巴瘤细胞 皮下部位导致肿瘤坏死消退， 疤痕 类似地，同时接种EBV永生化的B 细胞和伯基特淋巴瘤细胞在不同的皮下部位 导致伯基特氏肿瘤的一部分消退。 此外，大多数已建立的人类伯基特氏肿瘤都消退了， 肿瘤内接种EBV后出现坏死和瘢痕， 永生化B细胞。 EB病毒永生化B细胞继续发挥作用， 这种抗肿瘤作用甚至在被辐射杀死时也是如此。 的 伯基特淋巴瘤治疗的实验方法在这里描述 利用无胸腺小鼠排斥EBV永生化B细胞的能力 为了将有效的抗肿瘤反应靶向到恶性细胞， 无法引发它。 最近，我们开始研究 在本实验中， 系统 初步信息表明，一组鼠细胞因子 而肿瘤部位产生的趋化因子是导致肿瘤 回归分析

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. We considered the possibility that tumor cell killing might be induced by inoculation of the tumor-bearing host with benign cells which are normally destroyed if inoculated into the same host. We reasoned that by stimulating a local cytotoxic response in vivo one might achieve killing of tumor cells through a bystander effect. 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. Recently, we have began to study the mechanisms mediating Burkitt's lymphoma regression in this experimental system. Preliminary information suggests that a set of murine cytokines and chemokines produced at the tumor site are responsible for tumor regression.