IMMUNOTHERAPY FOR MALIGNANT GLIOMAS

恶性胶质瘤患者目前治疗的局限性， 与细胞因子的可用性一起， 免疫调节特性，已经引起了对免疫疗法的新兴趣。 这项研究的目的是确定潜在的有效方法， 免疫疗法的形式，以进一步研究在临床试验中。 这将是 通过检查人类神经胶质瘤组织中的因子， 有助于恶性胶质瘤逃避宿主免疫的能力 反应，并使用同系大鼠胶质瘤模型来评估各种 免疫治疗策略。 拟议的研究将包括两个部分： 1)人脑胶质瘤手术标本的免疫指标 （废弃组织），包括炎性 主要组织相容性复合体（MHC）的表达 抗原和辅助分子（LFA 3）将被检查 免疫细胞化学 这将提供一个标准， 在同基因大鼠胶质瘤模型中的免疫参数。 这些免疫 参数也将与临床和组织学特征相关。 假设MHC抗原和辅助抗原的相对缺乏， 分子和抑制诱导物CD 4+，2 H4+淋巴细胞的存在可能 有助于恶性胶质瘤逃避宿主的能力 将检查免疫应答。 2)一种反映免疫功能的同系大鼠脑胶质瘤模型 恶性胶质瘤的特征将用于评估各种 免疫治疗策略。 主要战略将涉及使用 增加肿瘤细胞上MHC的表达，使它们变得更 易受T细胞介导的免疫应答的影响。 其他战略 将被审查包括a）克服的影响， 胶质瘤细胞与白细胞介素-2释放的免疫抑制因子， 肿瘤坏死因子，B）增强淋巴因子激活的杀伤（LAK）细胞 和白细胞介素-2（IL-2）活性通过诱导HLA-DR在 c）使用针对消除肿瘤细胞的化疗， 抑制性T细胞

The limitation of current therapy for patients with malignant gliomas, together with the availability of cytokines with well defined immunomodulatory properties, have led to renewed interest in immunotherapy. The purpose of the proposed research is to identify potentially effective forms of immunotherapy for further study in clinical trials. This will be achieved by examining human glioma tissue for factors which may be contributing to the ability of malignant gliomas to evade the host immune response and using a syngeneic rat glioma model to evaluate various strategies of immunotherapy. The proposed research will consist of two parts: 1) The immune parameters within surgical specimens of human glioma tissue (discarded tissue), including the composition of the inflammatory infiltrate, and the expression of major histocompatibility complex (MHC) antigens and the accessory molecules (LFA 3) will be examined immunocytochemically. This will provide a standard for comparison with the immune parameters in the syngeneic rat glioma model. These immune parameters will also be correlated with clinical and histologic features. The hypothesis that the relative absence of MHC antigens and accessory molecules and the presence of suppressor inducer CD4+,2H4+ lymphocytes may be contributing to the ability of malignant gliomas to evade the host immune response will be examined. 2) A syngeneic rat glioma model which reflects the immunologic characteristics of malignant gliomas will be used to evaluate various strategies of immunotherapy. The principle strategy will involve the use of cytokines to increase MHC expression on tumor cells, rendering them more susceptible to T cell mediated immune responses. Additional strategies that will be examined include a) overcoming the effects of immunosuppressive factors released by glioma cells with interleukin-2 and tumor necrosis factor, b) augmenting lymphokine activated killer (LAK) cell and interleukin-2 (IL-2) activity by inducing HLA-DR expression on the tumor cells and c) using chemotherapy directed towards the elimination of suppressor T cells.