Adjuvant immunotherapy with tumor infiltrating lymphocytes and interleukin-2 in patients with resected stage III and IV melanoma

被引:18
作者
Ridolfi, L
Ridolfi, R
Riccobon, A
De Paola, F
Petrini, M
Stefanelli, M
Flamini, E
Ravaioli, A
Verdecchia, GM
Trevisan, G
Amadori, D
机构
[1] Pierantoni Hosp, Dept Med Oncol, I-47100 Forli, Italy
[2] IOR, Forli, Italy
[3] Morgagni Hosp, Dept Gen Surg, Forli, Italy
[4] Univ Trieste, Dept Dermatol, I-34127 Trieste, Italy
来源
JOURNAL OF IMMUNOTHERAPY | 2003年 / 26卷 / 02期
关键词
interleukin-2; melanoma; tumor-infiltrating lymphocytes;
D O I
10.1097/00002371-200303000-00008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) and interleukin (IL)-2 is reasonably effective in the treatment of patients with advanced melanoma. However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (resected stages III and IV). In a preliminary study, 25 patients (aged 23-72 years) with stage III-IV melanoma who underwent resection of metachronous metastases were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m(2)) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) evaluable patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) rates were 44% and 37%, respectively, at 2 years, and 52% and 45% at 3 years. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 X 10(6) versus 86 x 10(6) IU/m(2), respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. Analysis of tumor immunosuppression factors in lymphocytes inside the tumor (TCR xi and is an element of chains, p56(lck), FAS, and FAS-ligand) confirmed that the immunologic potential of TIL, depressed at the time of metastasectomy, was significantly restored after in vitro culture with IL-2. Adoptive immunotherapy with TIL and IL-2 could improve DFS and OS, although further work is required to determine its role in the treatment of patients with high-risk melanoma.
引用
收藏
页码:156 / 162
页数:7
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