Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients
Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients
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DOI：
10.1097/00002371-200307000-00005
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发表时间：
2003-07-01
影响因子：
3.9
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
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作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
产生对肿瘤抗原具有特异性反应的T淋巴细胞是有效过继转移治疗的先决条件。肿瘤浸润性淋巴细胞(TIL)可在高水平IL-2的体外培养条件下建立黑色素瘤特异性淋巴细胞培养。我们已经优化了从切除的小肿瘤标本中产生黑色素瘤反应性TIL培养的方法。我们报告了对62例人类白细胞抗原A2(+)患者的90例黑色素瘤连续活检标本中的860例TIL培养的回顾分析。来自单个肿瘤的多个独立的TIL通常表现出很大的功能和表型差异。在筛选的36例患者中，29例(81%)的TIL中检测到肿瘤特异性活性。被选为高活性的TIL培养物通常能够使用单轮快速扩增方案进行大规模数值扩增。在寡克隆性TIL培养中，有限的克隆性T细胞群可以在这些高度精选、高度扩增的TIL培养中提供特异性的肿瘤识别。这些方法在产生适合过继转移治疗的TIL方面是有效的。
The generation of T lymphocytes with specific reactivity against tumor antigens is a prerequisite for effective adoptive transfer therapies. Melanoma-specific lymphocyte cultures can be established from tumor infiltrating lymphocytes (TILs) by in vitro culture in high levels of IL-2. We have optimized methods for generating melanoma-reactive TIL cultures from small resected tumor specimens. We report a retrospective analysis of 860 attempted TIL cultures from 90 sequential melanoma biopsy specimens from 62 HLA-A2(+) patients. Multiple independent TIL derived from a single tumor often exhibited substantial functional and phenotypic variation. Tumor specific activity was detected in TIL from 29 (81%) of 36 patients screened. TIL cultures selected for high activity were generally capable of large numerical expansion using a single round of a rapid expansion protocol. Limited clonal T-cell populations in an oligoclonal TIL culture could confer specific tumor recognition in these highly selected, highly expanded TIL cultures. These methods were efficient at generating TILs suitable for adoptive transfer therapy.