Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma
Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma
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DOI：
10.1097/00002371-200107000-00012
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发表时间：
2001-07-01
影响因子：
3.9
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
--
作者：
Dudley, ME;Wunderlich, J;Rosenberg, SA
本报告描述了一项I期研究的过继转移克隆的黑色素瘤抗原特异性T淋巴细胞治疗晚期黑色素瘤患者。克隆来源于患者的外周血淋巴细胞或肿瘤浸润淋巴细胞，这些患者之前接受过黑素瘤相关抗原gp 100的免疫接种。在对其同源抗原的反应中，用于治疗的每个克隆分泌大量的干扰素-γ和粒细胞-巨噬细胞集落刺激因子，较少量的白细胞介素（IL）-2和TNF-α，以及很少或没有IL-4和IL-10。克隆也证明了识别人类白细胞抗原匹配的黑色素瘤细胞因子分泌和裂解测定。12名患者单独接受了2个周期的细胞; 11名患者接受了额外的细胞周期，并在两种IL-2方案之间随机分配（125，000 IU/kg皮下每日持续12天与720，000 IU/kg静脉内每8小时持续4天）。共给予51个周期的细胞，每个周期平均1 × 10（10）个细胞。通过T细胞受体特异性聚合酶链反应分析外周血样本中转移细胞的持久性。转移细胞在转移后11 t达到最大水平，但在2周时迅速下降至不可检测的水平。观察到1例轻微缓解和1例混合缓解（均在高剂量IL-2组中）。本报告证明了克隆T细胞转移作为癌症患者治疗的安全性和可行性。该方案缺乏临床有效性表明，成功治疗需要转移不同或额外的细胞类型或调节受体宿主环境。
This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gp100. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon-gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; I I patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 h for 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at I It after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional cell types or that modulation of the recipient host environment is required for successful therapy.