Dudley Mark E, Wunderlich John R, Shelton Thomas E, Even Jos, Rosenberg Steven A
Surgery Branch, National Cancer Institute, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA.
J Immunother. 2003 Jul-Aug;26(4):332-42. doi: 10.1097/00002371-200307000-00005.
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.
产生对肿瘤抗原有特异性反应的T淋巴细胞是有效的过继性转移疗法的前提条件。黑色素瘤特异性淋巴细胞培养物可通过在高水平白细胞介素-2中进行体外培养，从肿瘤浸润淋巴细胞（TIL）中建立。我们已经优化了从小的切除肿瘤标本中产生黑色素瘤反应性TIL培养物的方法。我们报告了对62例HLA-A2+患者的90份连续黑色素瘤活检标本进行的860次TIL培养尝试的回顾性分析。源自单个肿瘤的多个独立TIL通常表现出显著的功能和表型变异。在36例接受筛查的患者中，有29例（81%）的TIL检测到肿瘤特异性活性。选择具有高活性的TIL培养物通常能够使用一轮快速扩增方案进行大量的数量扩增。寡克隆TIL培养物中有限的克隆T细胞群体可在这些高度选择、高度扩增的TIL培养物中赋予特异性肿瘤识别能力。这些方法在产生适合过继性转移疗法的TIL方面是有效的。
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