Lee Y, Bigner D D
Neurol Clin. 1985 Nov;3(4):901-17.
Recent progress in brain tumor biology research has helped us to understand the causes of our failure to improve patient survival with current therapeutic approaches. Present combination regimens of surgery, radiotherapy, and chemotherapy fail to address adequately two inherent biologic properties of brain tumors: tumor-induced host immunosuppression and tumor cell heterogeneity. Future success in immunotherapy will depend on our ability to dissect the mechanisms involved in tumor-host interactions. Also, therapies may have to be individualized. The potential for MAs in research and clinical application is great owing to their unlimited discriminative power for molecular and functional characterization. Differential diagnosis of difficult cases, such as parenchymatous tumors or neoplastic cells in CSF, with panels of MAs will be available in the near future. The use of MAs to direct localization and therapy of brain tumors is also promising, as evidenced by the preliminary data from our laboratory and from those of other workers. Other applications of MAs, such as prevention of invasion and metastasis by targeting cell surface molecules involved in cell-matrix attachment function, are also under study. Future refinement in MA-specificity and in enhancement of MA-delivery to tumor sites will significantly complement new therapeutic approaches. As brain tumors evade immunosurveillance through active participation in inducing tumor-specific immunosuppression, successful immunotherapy, either passive serotherapy or active immunization, will be best achieved in patients with a slight or moderate immunosuppressive state. Alteration of immune status with various biologic response modifiers to boost host reactivity against tumors will be an important adjunct in our arsenal against brain tumors. IFNs, with their direct tumoricidal activity, and lymphokines (such as interleukin-2) may be such reagents with a promising future.
脑肿瘤生物学研究的最新进展帮助我们理解了为何当前的治疗方法未能提高患者生存率。目前手术、放疗和化疗的联合方案未能充分解决脑肿瘤的两个固有生物学特性：肿瘤诱导的宿主免疫抑制和肿瘤细胞异质性。免疫治疗未来的成功将取决于我们剖析肿瘤与宿主相互作用机制的能力。此外，治疗可能需要个体化。单克隆抗体（MAs）在研究和临床应用中的潜力巨大，因为它们对分子和功能特征具有无限的鉴别能力。在不久的将来，使用一组单克隆抗体对疑难病例进行鉴别诊断，如实质性肿瘤或脑脊液中的肿瘤细胞，将成为可能。正如我们实验室和其他研究人员的初步数据所示，使用单克隆抗体指导脑肿瘤的定位和治疗也很有前景。单克隆抗体的其他应用，如通过靶向参与细胞与基质附着功能的细胞表面分子来预防侵袭和转移，也在研究中。未来提高单克隆抗体的特异性以及增强其向肿瘤部位的递送，将显著补充新的治疗方法。由于脑肿瘤通过积极参与诱导肿瘤特异性免疫抑制来逃避免疫监视，因此在免疫抑制状态轻微或中度的患者中，被动血清疗法或主动免疫等成功的免疫治疗效果最佳。使用各种生物反应调节剂改变免疫状态以增强宿主对肿瘤的反应性，将成为我们对抗脑肿瘤武器库中的一项重要辅助手段。干扰素具有直接的杀肿瘤活性，淋巴因子（如白细胞介素 -2）可能是具有广阔前景的此类试剂。
