Gambacorti-Passerini C, Radrizzani M, Erba E, Fossati G, Parmiani G
Cancer Res. 1987 May 15;47(10):2547-52.
Six short term-cultured melanoma cell lines and one small cell lung cancer cell line were treated in vitro with the alkylating agent mafosfamide. The sensitivity of the surviving cells to in vitro lysis by recombinant interleukin 2-activated autologous and allogeneic lymphocytes was then investigated. In no case did chemo-surviving tumor cells appear less sensitive to lymphocyte-mediated lysis than untreated counterparts. In three of seven cases (two of which were derived from the same patient), chemo-selected cells were even more sensitive to cytotoxic lymphocytes, a difference not explained by a different distribution of neoplastic cells in the various cell cycle phases. We also studied the inhibitory activity of activated lymphocytes on the clonogenic potential of chemo-surviving tumor cells by the human tumor clonogenic assay. Inhibitions of tumor cell growth in the two patients tested were 100 and 94%, respectively; the activity of lymphocytes was dependent on the coculture time and the effector/target cell ratio. These data indicate that in vitro treatment with mafosfamide does not select cells resistant to the action of activated lymphocytes and that, given the right experimental conditions, these immune effectors can completely lyse tumor cells.
六种短期培养的黑色素瘤细胞系和一种小细胞肺癌细胞系在体外接受烷化剂马磷酰胺处理。然后研究存活细胞对重组白细胞介素2激活的自体和异体淋巴细胞体外裂解的敏感性。在任何情况下，化疗存活的肿瘤细胞对淋巴细胞介导的裂解的敏感性都不会低于未处理的对应细胞。在七个案例中的三个（其中两个来自同一患者）中，化疗选择的细胞对细胞毒性淋巴细胞甚至更敏感，这种差异不能用肿瘤细胞在不同细胞周期阶段的不同分布来解释。我们还通过人肿瘤克隆形成试验研究了活化淋巴细胞对化疗存活肿瘤细胞克隆形成潜力的抑制活性。在测试的两名患者中，肿瘤细胞生长的抑制率分别为100%和94%；淋巴细胞的活性取决于共培养时间和效应细胞/靶细胞比例。这些数据表明，体外使用马磷酰胺处理不会选择对活化淋巴细胞作用具有抗性的细胞，并且在合适的实验条件下，这些免疫效应细胞可以完全裂解肿瘤细胞。
