Ravaud A, Legrand E, Delaunay M M, Bussières E, Coulon V, Cany L, Huet S, Verdier D, Kind M, Chomy F
Department of Medical Oncology, Fondation Bergonié, Comprehensive Cancer Centre, Bordeaux, France.
Br J Cancer. 1995 Feb;71(2):331-6. doi: 10.1038/bjc.1995.66.
The aim of the protocol was to evaluate the side-effects induced by repeated tumour-infiltrating lymphocyte (TIL) infusions in patients with metastatic melanoma (MM). Patients were to receive four TIL infusions at given intervals: every 3 weeks (two patients), every 2 weeks (3 patients) and weekly (4 patients). All patients were evaluated and received a total of 34 TIL infusions. The total number of TILs administered varied from 0.65 to 2.34 x 10(11) cells. TIL phenotypes were predominantly CD8+ (two patients), CD4+ (4 patients), CD4+ then CD8+ (two patients) or CD56+ (two patient). Autocytotoxicity was only observed for one culture. Six patients presented at least one WHO grade 3 side-effect: hypotension (5 patients), dyspnoea (two patients), fever (one patient), fatigue (one patient), chills (two patients), diarrhoea (one patient), agitation (one patient), locoregional pain (two patients). Hypotension was constantly seen in patients who were given TILs every week. Two cases of minor pericarditis were recorded. No objective response to treatment was observed; 1 stable disease occurred in one patient and progression in eight. However, five patients presented a partial response on a tumour site for 1-4 months. Three patients presented signs of inflammation or softening at one tumour site. Plasma tumour necrosis factor alpha (TNF-alpha) levels were increased 1.2- to 22-fold after TIL infusion. TILs could be produced in sufficient quantity to perform this study, so repetitive infusions of TIL became possible on a weekly basis. However, no objective response was observed even when TIL infusions were performed weekly. An increase in circulating TNF-alpha was noted after TIL infusion.
该方案的目的是评估转移性黑色素瘤（MM）患者重复输注肿瘤浸润淋巴细胞（TIL）所引起的副作用。患者按给定间隔接受4次TIL输注：每3周（2例患者）、每2周（3例患者）和每周（4例患者）。所有患者均接受评估，共接受了34次TIL输注。给予的TIL总数在0.65至2.34×10¹¹个细胞之间。TIL表型主要为CD8⁺（2例患者）、CD4⁺（4例患者）、先CD4⁺后CD8⁺（2例患者）或CD56⁺（2例患者）。仅在一种培养物中观察到自细胞毒性。6例患者出现至少一种世界卫生组织3级副作用：低血压（5例患者）、呼吸困难（2例患者）、发热（1例患者）、疲劳（1例患者）、寒战（2例患者）、腹泻（1例患者）、激动（1例患者）、局部疼痛（2例患者）。低血压在每周接受TIL治疗的患者中持续出现。记录到2例轻度心包炎。未观察到对治疗的客观反应；1例患者病情稳定，8例患者病情进展。然而，5例患者在肿瘤部位出现了1至4个月的部分缓解。3例患者在一个肿瘤部位出现炎症或软化迹象。TIL输注后血浆肿瘤坏死因子α（TNF-α）水平升高了1.2至22倍。TIL能够大量生产以进行本研究，因此每周重复输注TIL成为可能。然而，即使每周进行TIL输注，也未观察到客观反应。TIL输注后循环TNF-α有所升高。
