Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations.
Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations.
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使用人重组白细胞介素 2 和活化的自体淋巴细胞进行恶性神经胶质瘤的免疫治疗。
DOI：
10.1007/bf00177842
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发表时间：
1990
影响因子：
3.9
通讯作者：
Young,HF
中科院分区：
文献类型：
--
作者：
Merchant,RE;Ellison,MD;Young,HF
在过去的几年里，我们和其他一些研究小组进行了实验室实验和临床试验，单独使用人重组白细胞介素-2（rIL-2）或与自体“活化”淋巴细胞联合使用，以确定毒性并表明其在高级别胶质瘤患者中的潜在疗效。由于高rIL-2浓度可以获得与毒性大大低于全身的方法，所有的临床试验，迄今为止，选择了直接的途径;注射淋巴因子和细胞到肿瘤组织，肿瘤切除后剩余的囊腔，和/或周围的肿瘤切除部位的神经实质。虽然rIL-2疗法，因为它们已经应用于动物胶质瘤模型和患者，是安全的，治疗部位周围的脑水肿一直是一个一致的发现。然而，我们也看到，患者用于控制脑水肿的类固醇药物可能通过抑制淋巴细胞产生正常LAK活性的能力而抑制rIL-2的抗肿瘤活性。尽管涉及rIL-2的免疫疗法均未产生治愈，但已报道的持续临床应答的事实表明，此类疗法可减缓治疗部位的肿瘤复发。改善恶性胶质瘤的基于rIL-2的免疫疗法的结果的努力正在继续进行，其中包括rIL-2给药和时间表的操作以及rIL-2和其他重组细胞因子的组合。
Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous ‘activated’ lymphocytes expressingin vitrotumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2 - based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines.