Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2.
Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2.
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DOI：
10.1084/jem.159.2.495
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发表时间：
1984-02-01
期刊：
影响因子：
--
通讯作者：
Rosenberg SA
中科院分区：
文献类型：
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作者：
Mazumder A;Rosenberg SA
在之前的体外研究中，我们已经表明，在 IL-2 中孵育的小鼠脾细胞或癌症患者淋巴细胞对新鲜的同基因或自体肿瘤具有溶解作用。我们现在已经在小鼠 B16 转移模型中进行了这种淋巴因子激活杀伤 (LAK) 细胞的过继转移，以测试其体内功效。将 1 X 10(8) LAK 细胞静脉注射到已形成 B16 肺转移的 C57BL/6 小鼠体内，可导致肺结节数量显着减少并提高生存率。患肿瘤肢体截肢后 3 天施用 LAK 细胞也降低了自发性肺转移的发生率。由荷瘤脾细胞产生的LAK细胞具有与正常动物相同的效果，并且LAK细胞的这种抗转移作用不需要事先施用环磷酰胺或其他免疫抑制剂。新鲜或未刺激的脾细胞没有影响。体内和体外的抗肿瘤效应物和前体是Thy-1+。激活所需的淋巴因子似乎是白细胞介素 2 (IL-2)，因为在来自 PMA 脉冲的 EL-4 或 Con A 脉冲的脾细胞或纯化的 Jurkat IL-2 的部分纯化的上清液中孵育，导致产生体内同样活跃的 LAK 细胞。 IL-2激活细胞的使用也可能为人类肿瘤的过继治疗提供一种有价值的方法。
In previous in vitro studies, we have shown that murine splenocytes or cancer patient lymphocytes incubated in IL-2 become lytic for fresh syngeneic or autologous tumors. We have now performed the adoptive transfer of such lymphokine-activated killer (LAK) cells in a murine B16 metastasis model to test their in vivo efficacy. 1 X 10(8) LAK cells, infused intravenously into C57BL/6 mice with established B16 pulmonary metastases, led to a marked decreased in the number of lung nodules and improved survival. LAK cells administered 3 d after amputation of a tumor-bearing limb also decreased the incidence of spontaneous pulmonary metastases. LAK cells generated from tumor-bearer splenocytes had effects equivalent to those from normal animals, and this antimetastatic effect of the LAK cells did not require the prior administration of cyclophosphamide or other immunosuppressants. Fresh or unstimulated splenocytes had no effect. The antitumor effectors and precursors in vivo and in vitro were Thy-1+. The lymphokine required for the activation appeared to be interleukin 2 (IL-2), since incubation in partially purified supernatants from PMA pulsed EL-4 or Con A-pulsed splenocytes or purified Jurkat IL-2 led to the generation of LAK cells equally active in vivo. The use of IL-2-activated cells may provide a valuable method for the adoptive therapy of human neoplasms as well.