Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases.
Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases.
复制标题
对自体黑色素瘤细胞具有特异性的人细胞毒性 T 细胞：连续七例从淋巴结细胞成功生成。
DOI：
10.1093/jnci/80.13.1016
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Seigler,HF
中科院分区：
文献类型：
--
作者：
SlingluffJr,CL;Darrow,T;Vervaert,C;Quinn-Allen,MA;Seigler,HF
人T细胞群特异性细胞毒性自体黑色素瘤细胞已成功地产生从淋巴结细胞获得的七个连续的患者。淋巴结细胞在体外用自体辐射黑色素瘤细胞刺激;每10-15天重复刺激，肿瘤细胞与淋巴细胞的比例为1：20。通过4小时51 Cr释放试验评估细胞毒性活性。在效应细胞与靶细胞比例为20：1时，自体肿瘤细胞的平均裂解率为47%，而人髓性白血病细胞系K562、同种异体黑色素瘤细胞和骨肉瘤细胞的平均裂解率分别为20%、13%和11%。自体成纤维细胞、新鲜淋巴细胞或植物血凝素刺激的原始细胞均未发生裂解。三个等级的特异性依次发展。在I级中，自体肿瘤细胞的裂解超过K562细胞和所有测试的同种异体肿瘤细胞的裂解。在III级中，自体肿瘤细胞的有效裂解（>40%）超过K562细胞和所有测试的同种异体肿瘤细胞的裂解。所有7个淋巴细胞群均达到或超过I级。六个达到或超过二级。两人升到三级。产生的细胞是T细胞，如通过流式细胞术的表型分析所确定的。CD 4+和CD 8+细胞占细胞总数的83%~ 100%。通过用0 KT 8和0 KT 4抗体淘选将⑶ 8 + T细胞与⑶ 4 + T细胞分离。在细胞毒性测定中将所得的富含CD 8+和富含CD 4的群体作为效应物进行比较。结果表明，负责溶解自体肿瘤细胞的细胞是CD 8+。本研究中使用的方法已多次导致成功产生对自体黑色素瘤细胞具有特异性细胞毒性的细胞毒性T淋巴细胞;这表明这些细胞具有用于黑色素瘤过继免疫治疗的潜在应用。[J Natl Cancer Inst 1988;80：1016-1026]
Human T-cell population specifically cytotyxic for autologous melanoma cells have been successfully generated from lymph node cells obtained from seven consecutive patients. The lymph node cells were stimulated in vitro with autologous irradiated melanoma cells; stimulation was repeated every 10–15 days at a tumor cell-to-lymphocyte ratio of ≈1:20. Cytotoxic activity was assessed by a 4-hour51Cr release assay. Mean lysis of autologous tumor cells was 47% at an effector-to-target cell ratio of 20:1, while mean lyses of the human myeloid leukemia cell line K562, allogeneic melanoma cells, and an osteosarcoma cell were 20%, 13%, and 11%, respectively. There was no lysis of autologous fibroblasts, fresh lymphocytes, or phytohemagglutinin stimulated blasts. Three grades of specifity developed sequentially. In grade I, lysis of autologous tumor cells exceed lysis of K562 cells and all allogeneic tumor cells tested. In grade III, potent lysis of autologous tumor cells(>40%) exceeded lysis of K562 cells and of all allogeneic tumor cells tested. All seven lymphocyte populations reached or exceeded grade I. Six reached or exceeded grade II. Two progressed to grade III. The generated cells were T cells, as determined by phenotypic analysis with flow cytometry. CD4+ cells and CD8+ cells accounted for 83%–100% of the cells. CD8+ T cells were separated from CD4+ T cells by panning with OKT8 and OKT4 antibodies. The resulting CD8+–enriched and CD4–enriched populations were compared as effectors in cytotoxicity assays. The results suggest that the cell responsible for lysis of autologous tumor cells is CD8+. The methods used in this study have repeatedly resulted in the successful generation of cytotoxic T lymphocytes specifycally cytotoxic for autologous melanoma cells; it is suggested that these cells have potential application for adoptive immunotherapy of melanoma. [J Natl Cancer Inst 1988;80:1016–1026]