Holladay F P, Heitz T, Chen Y L, Chiga M, Wood G W
Department of Pathology, University of Kansas Medical Center, Kansas City.
Neurosurgery. 1992 Sep;31(3):528-33. doi: 10.1227/00006123-199209000-00015.
Brain tumors are highly resistant to therapy. Their diffuse infiltrative nature and the relative inaccessibility of brain tissue to blood and lymph are barriers to surgical and cytotoxic treatments alike. The purpose of this study was to produce immune cells specifically reactive with an anaplastic rat glioma (RT2) and determine whether those cells could affect tumor progression in the brain. RT2-specific cytotoxic cells were prepared by priming rats in vivo with RT2 tumor cells and Corynebacterium parvum and stimulating the primed lymphocytes in vitro with irradiated RT2 tumor cells and interleukin-2 (IL-2). Cultured cells exhibited a high level of cytotoxicity against RT2, but not C6 (an allogeneic glioma), 3M2N (a syngeneic mammary tumor), or CSE (a syngeneic fibrosarcoma) tumor cells. To generate a model for therapy, rats were injected intracerebrally with RT2, generating progressing brain tumors, which killed untreated rats in approximately 2 weeks. To test the therapeutic potential of the effector cells, tumor-bearing rats were treated by intravenous injection of lymphocytes on Day 5 of tumor growth. Treated rats also received a 5-day course of systemic IL-2 beginning on Day 5. Treatment with IL-2 alone, RT2-primed spleen cells, or RT2-primed spleen cells stimulated in vitro with C6 did not affect rat survival. However, tumor-bearing rats treated with RT2-stimulated lymphocytes exhibited increased survival or were cured. Systemic IL-2 was an essential adjunct, because survival was not affected by treatment with effector cells alone. Therapy initiated on Day 8 of tumor progression lacked effect on survival.(ABSTRACT TRUNCATED AT 250 WORDS)
脑肿瘤对治疗具有高度抗性。其弥漫性浸润的特性以及脑组织相对难以通过血液和淋巴进行治疗，这对手术和细胞毒性治疗而言都是障碍。本研究的目的是制备与间变性大鼠胶质瘤（RT2）特异性反应的免疫细胞，并确定这些细胞是否能影响脑肿瘤的进展。通过在体内用RT2肿瘤细胞和短小棒状杆菌致敏大鼠，并在体外使用照射过的RT2肿瘤细胞和白细胞介素-2（IL-2）刺激致敏淋巴细胞，制备了RT2特异性细胞毒性细胞。培养的细胞对RT2表现出高水平的细胞毒性，但对C6（同种异体胶质瘤）、3M2N（同基因乳腺肿瘤）或CSE（同基因纤维肉瘤）肿瘤细胞没有细胞毒性。为了建立治疗模型，将RT2脑内注射到大鼠体内，形成进展性脑肿瘤，未治疗的大鼠在大约2周内死亡。为了测试效应细胞的治疗潜力，在肿瘤生长第5天通过静脉注射淋巴细胞对荷瘤大鼠进行治疗。治疗大鼠还从第5天开始接受为期5天的全身性IL-2治疗。单独使用IL-2、RT2致敏的脾细胞或用C6体外刺激的RT2致敏的脾细胞进行治疗，均不影响大鼠存活。然而，用RT2刺激的淋巴细胞治疗的荷瘤大鼠存活期延长或被治愈。全身性IL-2是必不可少的辅助治疗手段，因为单独使用效应细胞治疗不影响存活。在肿瘤进展第8天开始的治疗对存活没有影响。（摘要截断于250字）
