Quattrocchi K B, Miller C H, Cush S, Bernard S A, Dull S T, Smith M, Gudeman S, Varia M A
Division of Neurosurgery, University of North Carolina, Chapel Hill, USA.
J Neurooncol. 1999;45(2):141-57. doi: 10.1023/a:1006293606710.
A prospective pilot study was performed in order to assess the safety of treating recurrent malignant gliomas (MGs) with locally infused autologous tumor infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2). Six patients were entered between June 27, 1994 and June 2, 1995 and followed until July 1, 1998. At surgery an Ommaya reservoir was placed for later infusion of TILs and rIL-2. Following surgery, autologous TILs were expanded in vitro in the presence of rIL-2 and infused on treatment days 1 and 14, with concurrent rIL-2 infusions performed three times each week for one month. Following completion of immunotherapy all patients were offered chemotherapy. Phenotypic analysis demonstrated TILs to be T-lymphocytes (87-99% CD3+). Of these, 4 of 6 cases (67%) phenotyped as cytotoxic/suppressor T-lymphocytes (CD8+) and 2 of 6 cases (33%) phenotyped as helper/inducer T-lymphocytes (CD4+). TILs demonstrated limited selective cytotoxicity, with dose dependent cytotoxicity against autologous tumor, allogenic tumor and long term MG cell lines. There were no significant (Grade 3 or 4) complications. One patient developed transient low grade fevers, and 2 developed asymptomatic hydrocephalus. All patients developed transient and asymptomatic cerebral swelling, noted on the immediate post-treatment imaging studies. At three and six month follow-up, 3 patients responded with partial response, 2 demonstrated stable disease and 1 patient progressed. At long term follow-up, 1 patient had a complete response (45 month follow-up), 2 had a partial response (48 and 47 month follow-up) and 3 patients expired as a result of progressive disease (at 12, 12 and 18 months following immunotherapy). A relationship between subsequent chemotherapy or extent of resection to outcome was not apparent but could not be excluded. This pilot study demonstrated that locally infused autologous TILs and rIL-2 could be delivered without serious toxicity. Further studies are indicated to determine the safety and long term efficacy of TIL immunotherapy.
为了评估局部注入自体肿瘤浸润淋巴细胞（TILs）和重组白细胞介素-2（rIL-2）治疗复发性恶性胶质瘤（MGs）的安全性，进行了一项前瞻性试点研究。1994年6月27日至1995年6月2日期间纳入了6例患者，并随访至1998年7月1日。手术时放置了一个Ommaya储液器，以便日后注入TILs和rIL-2。手术后，自体TILs在rIL-2存在的情况下进行体外扩增，并在治疗第1天和第14天注入，同时每周进行3次rIL-2注入，持续1个月。免疫治疗完成后，所有患者均接受化疗。表型分析显示TILs为T淋巴细胞（87 - 99% CD3+）。其中，6例中有4例（67%）表型为细胞毒性/抑制性T淋巴细胞（CD8+），6例中有2例（33%）表型为辅助/诱导性T淋巴细胞（CD4+）。TILs显示出有限的选择性细胞毒性，对自体肿瘤、同种异体肿瘤和长期MG细胞系具有剂量依赖性细胞毒性。没有显著（3级或4级）并发症。1例患者出现短暂的低热，2例出现无症状性脑积水。所有患者在治疗后即刻的影像学检查中均出现短暂的无症状性脑肿胀。在3个月和6个月的随访中，3例患者有部分缓解反应，2例病情稳定，1例患者病情进展。在长期随访中，1例患者完全缓解（随访45个月），2例部分缓解（随访48个月和47个月），3例患者因疾病进展死亡（免疫治疗后12、12和18个月）。后续化疗或切除范围与预后之间的关系不明显，但不能排除。这项试点研究表明，局部注入自体TILs和rIL-2可以在没有严重毒性的情况下进行。需要进一步研究以确定TIL免疫治疗的安全性和长期疗效。
