Kataoka T, Ogihara K, Sakurai Y
Cancer Res. 1980 Oct;40(10):3839-45.
The combined administration of mitomycin C (MMC) on Day 5 and concanavalin A (Con A)-bound L1210 murine leukemia vaccine on Days 1 and 8 induced an enhanced therapeutic response in animals bearing L1210 leukemia greater than that inducible by either of them. The enhancement was dependent on the administration timing of the vaccine, dependent on vaccine-bound Con A, and specific for L1210 leukemia, as evidenced by the fact that no enhancement was induced in P388 leukemic animals. However, the enhancement was dependent on delayed MMC administration, and MMC administered on Day 3 failed to induce the enhancement, indicating that the chemotherapeutic potency of MMC played no major role in the enhancement. These results suggest that the enhancement may be dependent on antileukemia immunity induced by Con A-bound vaccine and may be further potentiated by MMC. A series of experiments comparing immunoprophylactic and immunotherapeutic responses inducible by different chemotherapeutic agents combined with the vaccine suggested that chemotherapeutic agents enhanced the potency of the vaccine by abrogating suppressors associated with vaccine-bound Con A. This hypothesis was supported by the finding that tumor vaccine induced peritoneal cells of tumor-bearing animals were abrogated in their suppressor activity in polyclonal in vitro spleen cell blastogenesis when these animals were further treated with MMC.
在第5天联合给予丝裂霉素C（MMC），并在第1天和第8天给予伴刀豆球蛋白A（Con A）结合的L1210小鼠白血病疫苗，可使携带L1210白血病的动物产生比单独使用其中任何一种药物时更强的治疗反应。这种增强作用取决于疫苗的给药时间，取决于与疫苗结合的Con A，并且对L1210白血病具有特异性，这一点可由P388白血病动物未出现增强作用得到证明。然而，这种增强作用取决于MMC的延迟给药，在第3天给予MMC未能诱导出增强作用，这表明MMC的化疗效力在增强作用中未起主要作用。这些结果表明，这种增强作用可能取决于与Con A结合的疫苗诱导的抗白血病免疫，并且可能会被MMC进一步增强。一系列比较不同化疗药物与疫苗联合诱导的免疫预防和免疫治疗反应的实验表明，化疗药物通过消除与结合Con A的疫苗相关的抑制因子来增强疫苗的效力。这一假设得到了以下发现的支持：当荷瘤动物进一步接受MMC治疗时，肿瘤疫苗诱导的荷瘤动物腹腔细胞在多克隆体外脾细胞增殖反应中的抑制活性被消除。
