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[中枢神经系统肿瘤的免疫治疗]

[Immunotherapy of tumors of the central nervous system].

作者信息

Monod L, Sawamura Y, De Tribolet N

机构信息

Service de neurochirurgie, Centre Hospitalier Universitaire Vaudois, Lausanne.

出版信息

Neurochirurgie. 1992;38(2):69-79.

PMID:1603233
Abstract

Malignant brain tumors are rapidly fatal and adjunction of chemo- and radio-therapy to surgical treatment has little changed their poor prognosis. The development of basic and clinical research in immunology of brain tumors has lead to new therapeutic strategies: 1) Humoral factors: Monoclonal antibodies (MAbs): alone or conjugated (to toxins, radionucleides or chemotherapeutic agents), MAbs can theoretically recognize antigens expressed by tumor cells and reach this target with high specificity. Large amounts of tumoricidal agents could be given to the tumor with low toxic effects to normal tissues. 2) Cellular factors: LAK cells: (lymphokine-activated-killer-cells) and activated TILs (tumor-infiltrating-lymphocytes) are autologous cytotoxic cells which can be produced by ex-vivo culture techniques and infused to the patient. These are very potent tumor-killer cells in vitro, however their in vivo effect is far less dramatic at the moment. 3) Cytokines: interferons, interleukins and other biological modifiers can act either directly on the tumor cells (cytotoxic effect) or indirectly through the modulation of the host-to-tumor response. 4) Combination of humoral and cellular factors: bispecific monoclonal antibodies are hybrid-molecules built from two different MAbs which can recognize two different targets, usually a tumor antigen on one hand and the T-cell-receptor (T 3) on the other hand. This combination of humoral and cellular effectors can theoretically lead to a preferential binding of effector cells to the tumor. All these new techniques are extensively studied in research laboratories and clinical trials without clear therapeutical benefit for the moment.

摘要

恶性脑肿瘤进展迅速且致命,手术治疗联合化疗和放疗几乎无法改变其不良预后。脑肿瘤免疫基础和临床研究的发展带来了新的治疗策略:1)体液因子:单克隆抗体(MAbs):单独使用或与毒素、放射性核素或化疗药物偶联,理论上MAbs能够识别肿瘤细胞表达的抗原,并以高特异性靶向该目标。可将大量杀肿瘤剂作用于肿瘤,而对正常组织的毒性作用较低。2)细胞因子:LAK细胞(淋巴因子激活的杀伤细胞)和活化的TILs(肿瘤浸润淋巴细胞)是自体细胞毒性细胞,可通过体外培养技术产生并注入患者体内。这些细胞在体外是非常有效的肿瘤杀伤细胞,但目前它们在体内的效果远没有那么显著。3)细胞因子:干扰素、白细胞介素和其他生物调节剂可直接作用于肿瘤细胞(细胞毒性作用),或通过调节宿主对肿瘤的反应间接发挥作用。4)体液和细胞因子联合:双特异性单克隆抗体是由两种不同的MAbs构建的杂交分子,可识别两个不同的靶点,通常一个是肿瘤抗原,另一个是T细胞受体(T3)。体液和细胞效应物的这种联合理论上可导致效应细胞优先与肿瘤结合。目前,所有这些新技术都在研究实验室和临床试验中进行了广泛研究,但尚未取得明确的治疗效果。

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1
[Immunotherapy of tumors of the central nervous system].[中枢神经系统肿瘤的免疫治疗]
Neurochirurgie. 1992;38(2):69-79.
2
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