CELLULAR IMMUNOLOGY

过继细胞免疫疗法的使用具有合理的疗效(10- 20%)抗转移性系统性癌症，主要是恶性黑色素瘤和 肾细胞癌。我们已经测试了这种疗法的疗效 成人原发恶性胶质瘤，结果令人鼓舞。东道主 以及决定这种治疗方式有益效果的肿瘤因素， 然而，人们对此知之甚少。这个项目的总体目标是 激活内源性自然杀伤细胞(NK)增强肿瘤细胞杀伤作用 细胞活性和高溶解效应细胞的过继转移。 使用多种激活细胞因子的特定单抗 可能会进一步增强针对初级大脑的细胞免疫反应 肿瘤。我们将尝试鉴定和表征细胞表面 促进自然杀伤细胞和/或淋巴因子激活的分子 杀伤细胞(LAK)介导的原发脑免疫识别和杀伤 用分离的NK/LAK耐药肿瘤克隆体外肿瘤和胶质瘤 椭球体。脑肿瘤克隆将来自成人和儿童 研究脑肿瘤对NK和LAK细胞的耐药机制。抗体 针对生长因子受体(如EGF-R)、癌基因蛋白 (例如，erbB2)或整合素黏附分子(例如，VCAM、VLA-4)将 测试以确定它们对肿瘤细胞是积极的还是消极的影响 细胞溶解。此外，我们将尝试增强免疫反应，以 使用细胞因子的原发脑肿瘤(例如干扰素-β、肿瘤坏死因子-α、白介素1、白介素6 增加肿瘤对裂解和抗体依赖细胞的敏感性 细胞毒性(ADCC)。

Adoptive cellular immunotherapy has been used with reasonable efficacy (10- 20%) against metastatic systemic cancers, primarily malignant melanoma and renal cell carcinoma. We have tested the efficacy of this therapy in adults with primary malignant glioma with encouraging results. The host and tumor factors that determine the beneficial effect of this modality, however, are poorly understood. the overall goal of this project is to augment the tumor cell killing by activating endogenous natural killer (NK) cell activity and the adoptive transfer of highly lytic effector cells. The use of multiple, activating cytokines of specific monoclonal antibodies may further potentiate the cellular immune response against primary brain tumors. We will attempt to identify and characterize cell surface molecules that facilitate natural killer cell and/or lymphokine activated killer (LAK) cell-mediated immune recognition and killing of primary brain tumors in vitro by using isolated NK/LAK resistant tumor clones, and glioma spheroids. Brain tumor clones will be derived from adult and pediatric brain tumors to study mechanisms of NK and LAK cell resistance. Antibodies directed against growth factor receptors (e.g. EGF-R), oncogene proteins (e.g. erbB2) or integrin adhesion molecules (e.g. VCAM, VLA-4) will be tested to determine if they positively or negatively affect tumor cell cytolysis. In addition, we will attempt to augment the immune response to primary brain tumors using cytokines (eg. IFN-beta, TNF-alpha, IL-1, IL-6) to increase tumor susceptibility to lysis, and antibody dependent cellular cytotoxicity (ADCC).