Nakamura O, Takakura K
No To Shinkei. 1982 Apr;34(4):333-9.
At present, nonspecific immunotherapy using BCG or Picibanil is popular as an immunotherapy for malignant brain tumor. On the other hand, specific immunotherapy using lymphocytes which play an important role in the passive transmission of tumor immunity is also performed. But this therapy has some disadvantage such as the problem of blocking factor or histocompatibility. To compensate for this disadvantage, specific immunotherapy using the chemical mediater, immune RNA, extracted from immunized lymphocytes has started. We extracted immune RNA from the spleen of immunized rat using phenol and SDS, and observed the effect of normal lymphocytes preincubated with immune RNA in vitro and in vivo experiments. In in vitro experiment, following results were obtained. (1) Normal lymphocytes incubated with immune RNA revealed a significant cytotoxicity and this effect was disappeared by the pretreatment of immune RNA with RNase. (2) Cytotoxic effect of immune RNA seemed to be a tumor specific response. (3) Not only syngeneic RNA, but also xenogeneic RNA were effective. In addition to these results, we decided the optimal condition in which immune RNA transferred the cell mediated cytotoxicity to normal lymphocytes. Next, we tried the purification of immune RNA by way of sucrose density gradient centrifugation method and oligo (dT) cellulose affinity chromatography method. Active fraction of immune RNA was contained in 8-16 S fraction and in poly (A) containing fraction. As in vivo experiment, we injected immune RNA incubated lymphocytes intravenously to brain tumor-bearing rats and observed for death daily. In this experiments, significant prolongation of mean survival time was recognized in the group treated with immune RNA. We now consider the clinical application of immune RNA for malignant brain tumor by the following method: immune RNA is obtained from the lymphocytes of sheep which has immunized with patient's tumor cells. And then patient's own lymphocytes strengthened by incubation with immune RNA is injected intratumorally by way of Ommaya's reservoir. To do this therapy safely and effectively, further purification of immune RNA and solution of its physiochemical characteristics will be necessary.
目前，使用卡介苗或沙培林的非特异性免疫疗法作为恶性脑肿瘤的免疫疗法很受欢迎。另一方面，也进行了使用在肿瘤免疫的被动传递中起重要作用的淋巴细胞的特异性免疫疗法。但这种疗法存在一些缺点，如阻断因子或组织相容性问题。为弥补这一缺点，已开始使用从免疫淋巴细胞中提取的化学介质免疫RNA进行特异性免疫疗法。我们用苯酚和十二烷基硫酸钠从免疫大鼠的脾脏中提取免疫RNA，并在体外和体内实验中观察了与免疫RNA预孵育的正常淋巴细胞的效果。在体外实验中，得到了以下结果。（1）与免疫RNA孵育的正常淋巴细胞显示出显著的细胞毒性，并且这种作用通过用核糖核酸酶预处理免疫RNA而消失。（2）免疫RNA的细胞毒性作用似乎是一种肿瘤特异性反应。（3）不仅同基因RNA，而且异种基因RNA都是有效的。除了这些结果，我们还确定了免疫RNA将细胞介导的细胞毒性传递给正常淋巴细胞的最佳条件。接下来，我们尝试通过蔗糖密度梯度离心法和寡聚（dT）纤维素亲和层析法纯化免疫RNA。免疫RNA的活性部分包含在8-16S部分和含聚（A）部分中。在体内实验中，我们将免疫RNA孵育的淋巴细胞静脉注射到荷脑肿瘤大鼠体内，并每天观察其死亡情况。在这个实验中，在用免疫RNA治疗的组中，平均存活时间有显著延长。我们现在考虑通过以下方法将免疫RNA临床应用于恶性脑肿瘤：免疫RNA从用患者肿瘤细胞免疫的绵羊的淋巴细胞中获得。然后，通过奥马亚储液器将经免疫RNA孵育增强的患者自身淋巴细胞瘤内注射。为了安全有效地进行这种治疗，进一步纯化免疫RNA并解决其理化特性问题将是必要的。
