Tsurushima H, Liu S Q, Tuboi K, Matsumura A, Yoshii Y, Nose T, Saijo K, Ohno T
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki.
Jpn J Cancer Res. 1999 May;90(5):536-45. doi: 10.1111/j.1349-7006.1999.tb00781.x.
Autologous cytotoxic T lymphocytes (CTL) against primary-cultured malignant gliomas were generated from peripheral blood mononuclear cells in vitro in 4 patients. Activities of the CTL were highly specific to the corresponding autologous glioma and were inhibited, in one patient, with antibodies against CD3, CD8 and MHC-class I molecules. When the CTL were injected 3 times into the primary-tumor-resected cavity via an Ommaya tube, reduction of the recurrent tumors with magnetic resonance imaging (MRI)-measured volumes exceeding 45 cm3 was observed in 3 patients. In a patient with glioblastoma multiforme (GBM), the tumor volume (estimated, 130 cm3) was rapidly reduced to 1/3, although re-recurrence of the tumor followed 40 days later. A slight but distinct rapid reduction of the tumor volume was observed in another GBM patient and in an anaplastic astrocytoma patient; essentially no change was observed in a further GBM patient. These results suggest that adoptive immunotherapy with autologous CTL will be clinically effective against end-stage malignant gliomas.
从4例患者的外周血单个核细胞体外培养出针对原代培养恶性胶质瘤的自体细胞毒性T淋巴细胞(CTL)。CTL的活性对相应的自体胶质瘤具有高度特异性,在1例患者中,其活性被抗CD3、CD8和MHC-I类分子的抗体所抑制。当通过Ommaya管将CTL分3次注入原发性肿瘤切除腔时,3例患者经磁共振成像(MRI)测量,复发性肿瘤体积减少超过45 cm³。在1例多形性胶质母细胞瘤(GBM)患者中,肿瘤体积(估计为130 cm³)迅速缩小至1/3,尽管40天后肿瘤再次复发。在另1例GBM患者和1例间变性星形细胞瘤患者中观察到肿瘤体积有轻微但明显的快速缩小;在另1例GBM患者中基本未观察到变化。这些结果表明,自体CTL过继性免疫治疗对晚期恶性胶质瘤具有临床疗效。