A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency.
A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency.
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DOI：
10.4049/jimmunol.153.4.1687
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发表时间：
1994-08
影响因子：
4.4
通讯作者：
P. Lu;R. Negrin
中科院分区：
文献类型：
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作者：
P. Lu;R. Negrin
最近，我们报道了一种新的方案，通过在ifn - γ、IL-2、抗CD3单抗和IL-1 α存在下培养pbl，产生高效的细胞毒性效应细胞。我们将这些培养物命名为细胞因子诱导杀伤（CIK）细胞，因为具有最大细胞毒性的细胞表型同时表达T细胞标记CD3和NK细胞标记CD56。具有这种表型的细胞在未培养的pbl中是罕见的（约1 - 5%）。CD3+CD56+细胞在这些培养条件下扩增近1000倍。CIK培养中大多数CD3+CD56+细胞毒性细胞来源于CD3+CD56- T细胞，而不是CD3-CD56+ NK细胞。CD56而非CD8在CD3+细胞上的表达与对各种细胞靶标的最大细胞毒性相关。我们用严重联合免疫缺陷（SCID）小鼠注射人淋巴瘤细胞来评估CIK对淋巴因子激活杀伤（LAK）细胞的体内抗肿瘤作用。接种1 × 10(6)个SU-DHL4细胞（一种具有t（14;18）染色体易位的人B淋巴瘤细胞系），1天后静脉注射CIK细胞，与单独注射肿瘤细胞的对照动物（中位生存期90天vs 58天，p < 0.001）或LAK细胞治疗的动物（中位生存期90天vs 68天，p < 0.002）相比，各组动物的生存期明显延长。用SU-DHL4细胞攻击并用CIK细胞治疗的SCID小鼠中，约有30%成为长期幸存者，而用LAK细胞治疗的小鼠则没有。6个月后，用t(14;18) PCR分析CIK细胞治疗的长期幸存者的骨髓、脾脏、肝脏和肺部时，未发现隐匿性淋巴瘤的分子证据。在这些培养条件下，与LAK细胞相比，SCID小鼠体内具有优越抗肿瘤活性的t细胞可以很容易地产生新的细胞毒性细胞群。
Recently, we have reported a novel protocol for the generation of highly efficient cytotoxic effector cells by culturing PBLs in the presence of IFN-gamma, IL-2, mAb against CD3, and IL-1 alpha. We have termed these cultures cytokine-induced killer (CIK) cells because the phenotype of the cells with the greatest cytotoxicity expresses both the T cell marker CD3 and the NK cell marker CD56. Cells with this phenotype are rare (approximately 1 to approximately 5%) in uncultured PBLs. CD3+CD56+ cells expand nearly 1000-fold under these culture conditions. The majority of the CD3+CD56+ cytotoxic cells in CIK cultures were derived from CD3+CD56- T cells, and not CD3-CD56+ NK cells. Expression of CD56, but not CD8, on CD3+ cells correlated with the greatest cytotoxicity against various cellular targets. We have used mice with severe combined immunodeficiency (SCID) injected with human lymphoma cells to evaluate the in vivo antitumor effects of CIK vs lymphokine-activated killer (LAK) cells. Groups of animals inoculated with 1 x 10(6) SU-DHL4 cells (a human B lymphoma cell line with a t(14;18) chromosomal translocation), injected 1 day later with CIK cells either i.v. or i.p., had significantly prolonged survival compared with control animals injected with tumor cells alone (median survival 90 days vs 58 days, p < 0.001) or animals treated with LAK cells (median survival 90 days vs 68 days, p < 0.002). Approximately 30% of the SCID mice challenged with SU-DHL4 cells and treated with CIK cells became long-term survivors compared with none of the animals treated with LAK cells. No molecular evidence of occult lymphoma was found in the CIK cell-treated long-term survivors when their bone marrow, spleen, liver, and lung were analyzed by t(14;18) PCR at the end of 6 mo. By using these culture conditions, a novel population of cytotoxic cells can be generated readily from T cells that have superior in vivo antitumor activity in SCID mice, as compared with LAK cells.