Gautam S C, Chikkala N F, Lewis I, Grabowski D R, Finke J H, Ganapathi R
Research Institute, Cleveland Clinic Foundation, OH 44195.
Anticancer Res. 1992 May-Jun;12(3):921-5.
Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.
多药耐药（MDR）的产生仍然是癌症化疗失败的主要原因。在我们探索多药耐药肿瘤替代治疗方案的过程中，我们研究了多药耐药肿瘤细胞系对淋巴因子激活的杀伤（LAK）细胞的敏感性。对阿霉素（ADM）耐药的B16-BL6黑色素瘤、L1210和P388白血病细胞系进行了体外对LAK细胞裂解敏感性的测试。虽然发现对ADM耐药的B16-BL6和L1210亚系对LAK细胞裂解的敏感性至少高2倍，但对ADM耐药的P388细胞的敏感性与亲代细胞相似。由于对ADM耐药的B16-BL6细胞在体外能被LAK细胞有效裂解，因此评估了LAK细胞对体内对ADM耐药的B16-BL6亚系的治疗效果。与携带亲代B16-BL6肿瘤细胞的小鼠相比，LAK细胞和重组白细胞介素2（rIL2）的过继转移显著减少了携带对ADM耐药的B16-BL6肿瘤细胞小鼠的实验性转移形成（P<0.009），并延长了其平均生存时间（P<0.001）。结果表明，用LAK细胞和rIL2进行免疫治疗可能是治疗具有MDR表型癌症的一种有效方法。
