REGRESSION OF EXPERIMENTAL BURKITT'S LYMPHOMA IN ATHYMIC MICE

特异性转导淋巴细胞或肿瘤细胞的给药 细胞因子基因代表了治疗癌症的新方法。通过 要么提供抗肿瘤效应细胞，要么刺激抗肿瘤 在肿瘤部位的免疫这些实验模式导致了 一些现有肿瘤的成瘤性和退行性降低 实验模型。最近，逆转录病毒介导的体内转移 疱疹病毒来源的胸苷激酶(Tk)基因进入一定比例的脑内 胶质瘤细胞对一种抗病毒药物的破坏敏感 毒品。它还导致了其他肿瘤细胞的死亡，而不是通过 TK基因，通过一种不明确的旁观者效应。尽管如此， 实验结果，效应淋巴细胞的靶向性以及 抗肿瘤细胞因子与特定肿瘤的药物敏感因子 SITS的临床应用有限，因为它涉及到相对 复杂的程序并不广泛使用。 当皮下注射受照射的裸鼠时，人B组 被EB病毒(EBV)永生化的细胞要么不能生长，要么 长出小肿瘤，很快就会通过坏死和疤痕消退。 这种回归的机制还没有完全了解，但已经被 归因于残留的宿主免疫力。在同一实验系统中， 人Burkitt淋巴瘤细胞一般发展为致死性恶性 肿瘤。 在本研究中，我们检查了接种EB病毒是否永生。 B细胞可能对实验性Burkitt‘s有抗肿瘤作用 无瘤小鼠的淋巴瘤。EB病毒永生化B细胞同时接种的研究 细胞和Burkitt淋巴瘤细胞在同一皮下部位导致 随着坏死和疤痕的形成而退化的肿瘤。同样， EB病毒永生化B细胞和Burkitt氏细胞的同时接种 不同皮下部位的淋巴瘤细胞导致A 伯基特肿瘤的比例。此外，大多数已建立的 人Burkitt瘤术后坏死和疤痕消退 瘤内接种EB病毒永生化的B细胞。EBV- 永生化的B细胞继续发挥这种抗肿瘤作用 死于辐射。Burkitt淋巴瘤的实验研究 这里描述的治疗方法利用了无菌小鼠排斥反应的能力 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.