Hercend T, Farace F, Baume D, Charpentier F, Droz J P, Triebel F, Escudier B
Laboratoire d'Hémato-Immunologie, INSERM U333, Institut Gustave Roussy, Villejuif, France.
J Biol Response Mod. 1990 Dec;9(6):546-55.
Clinical immunotherapy trials have been performed recently where ex vivo interleukin-2 (IL-2)-activated peripheral blood mononuclear cells (i.e., the "LAK" cells) have been transfused in addition to IL-2 infusions. In such protocols, patients have received highly heterogeneous cell suspensions and the nature of the effector cells that may have contributed to tumor regression has remained unclear. In certain animal models, it has appeared that natural killer lymphocytes were the effector cell type responsible for tumor regression. To test whether NK cells could eventually be relevant for the treatment of human tumors, we have performed a feasibility trial where purified lymphokine-activated natural killer (LANAK) cells have been prepared and transfused to a limited series of renal cell carcinoma patients receiving IL-2 (continuous infusions at 3 x 10(6) U/m2/day). Natural killer lymphocytes (1-2 x 10(6] were purified from peripheral blood mononuclear cells and expanded during 4-5 weeks in the presence of IL-2 on microtiter plates containing feeder layers cells. In vitro, the resulting LANAK cell suspensions were 100 times (range of 2 to 10(3] more efficient against Daudi target cells than their autologous LAK counterparts. Twelve patients were included; 9 received the two planned courses of treatment with LANAK cells and IL-2. Overall toxicity was relatively moderate. Besides occasional chills, there were no apparent secondary effects due to cell infusions. The mean number of LANAK cells transfused per patients was 45.1 x 10(9), ranging from 7 to 125 x 10(9). The biodistribution of LANAK cells was similar to that reported previously for LAK cells with no preferential localization to tumor sites. We conclude from this study that using well-defined populations of effector lymphocytes is a feasible cellular therapy approach that may lead to improved understanding and efficacy of the novel immunotherapy methods.
最近开展了临床免疫治疗试验，除输注白细胞介素 -2（IL -2）外，还输注了体外经IL -2激活的外周血单个核细胞（即“LAK”细胞）。在这类方案中，患者接受的是高度异质性的细胞悬液，而可能促成肿瘤消退的效应细胞的性质仍不明确。在某些动物模型中，似乎自然杀伤淋巴细胞是负责肿瘤消退的效应细胞类型。为了测试自然杀伤细胞（NK细胞）最终是否与人类肿瘤的治疗相关，我们进行了一项可行性试验，制备了纯化的淋巴因子激活的自然杀伤（LANAK）细胞，并将其输注给了有限数量的接受IL -2（以3×10⁶U/m²/天持续输注）的肾细胞癌患者。从外周血单个核细胞中纯化出自然杀伤淋巴细胞（1 - 2×10⁶），并在含有饲养层细胞的微量滴定板上于IL -2存在的情况下扩增4 - 5周。在体外，所得的LANAK细胞悬液对Daudi靶细胞的杀伤效率比其自体LAK细胞悬液高100倍（范围为2至10³倍）。纳入了12名患者；9名患者接受了计划的两个疗程的LANAK细胞和IL -2治疗。总体毒性相对较轻。除偶尔出现寒战外，未观察到因细胞输注导致的明显副作用。每位患者输注的LANAK细胞的平均数量为45.1×10⁹，范围为7至125×10⁹。LANAK细胞的生物分布与先前报道的LAK细胞相似，未优先定位于肿瘤部位。我们从这项研究得出结论，使用明确界定的效应淋巴细胞群体是一种可行的细胞治疗方法，可能有助于更好地理解新型免疫治疗方法并提高其疗效。
