EXPANSION OF HUMAN-TUMOR INFILTRATING LYMPHOCYTES FOR USE IN IMMUNOTHERAPY TRIALS
EXPANSION OF HUMAN-TUMOR INFILTRATING LYMPHOCYTES FOR USE IN IMMUNOTHERAPY TRIALS
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DOI：
10.1016/s0022-1759(87)80018-2
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发表时间：
1987-08-24
影响因子：
2.2
通讯作者：
ROSENBERG, SA
中科院分区：
文献类型：
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作者：
TOPALIAN, SL;MUUL, LM;ROSENBERG, SA
小鼠实验表明肿瘤浸润淋巴细胞 (TIL) 在人类肿瘤过继免疫治疗中的潜在用途，显示这些细胞在治疗晚期转移性疾病方面比 LAK 细胞强 50-100 倍。本报告描述了一种大规模扩增人类 TIL 的方法，以便在临床试验中使用这些细胞。 TIL 在 25 个连续人类肿瘤中的 24 个中成功地以实验规模扩增，其中包括 6 种黑色素瘤、10 种肉瘤和 8 种腺癌。酶消化肿瘤以产生单细胞悬浮液，将其培养在含有10％人血清和1000U/ml重组白细胞介素2的RPMI 1640培养基中。淋巴细胞占单细胞肿瘤悬浮液的3%至74%，并且扩增从2.9倍至9.1倍。在 14 至 100 天的培养期内，增加了 108 倍。在 4 小时铬释放测定中，24 个 TIL 培养物中有 9 个裂解了新鲜的自体肿瘤靶标。细胞表面表型分析将培养的 TIL 鉴定为活化的细胞毒性/抑制性 T 细胞。随后，TIL 的大规模扩增在连续 8 个病例中的 5 个中成功产生了超过 1010 个淋巴细胞。采用扩大的 TIL 过继转移至转移性疾病患者的临床试验已经开始。
The potential utility of tumor-infiltrating lymphocytes (TIL) in the adoptive immunotherapy of human tumors has been suggested by murine experiments showing these cells to be 50-100 times more powerful than LAK cells in treating advanced metastatic disease. A method for the large-scale expansion of human TIL for the use of these cells in clinical trials is described in this report. TIL were successfully expanded on an experimental scale from 24 of 25 consecutive human tumors, including six melanomas, ten sarcomas, and eight adenocarcinomas. Tumors were digested enzymatically to yield single cell suspensions which were cultured in RPMI 1640 medium with 10% human serum and 1000 U/ml recombinant interleukin-2. Lymphocytes constituted from 3% to 74% of single cell tumor suspensions, and expanded from 2.9-fold to 9.1 .times. 108-fold over a culture period ranging from 14 to 100 days. Nine of 24 TIL cultures lysed fresh autologous tumor targets in 4 h chromium release assays. Cell surface phenotyping identified cultured TIL as activated cytotoxic/suppressor T cells. Subsequently, large-scale expansion of TIL was successful in generating more than 1010 lymphocytes in five of eight consecutive cases. Clinical trials employing the adoptive transfer of expanded TIL to patients with metastatic disease have begun.