Stark Y, Leibovici J, Wolman M
Int J Immunopharmacol. 1983;5(4):289-97. doi: 10.1016/0192-0561(83)90031-0.
Combined treatment with levan and cyclophosphamide (CY) was applied intratumorally to Lewis lung carcinoma tumors in C57B1 mice on day 5 after tumor cell inoculation. Although on that day levan alone had no effect and CY alone caused only temporary regression of tumors, the combined CY-levan treatment caused 60% cure. Levan given before CY was almost as effective as simultaneous administration of both drugs on day 5. Delaying the administration of levan after CY treatment reduced the therapeutic effect. It is concluded that timing in relation to tumor cell inoculation as well as the order of administration of drugs, determine the degree of therapeutic efficacy. In tumor chemo-immunotherapy the final effect is probably due not only to the anti-tumoral effect per se of each drug, but also to the fact that the two agents have an effect on the immune system. Since the immune response may change during tumor development, the effect of timing of administration of an immunomodulator and certainly to two immunomodulators, can be crucial.
在肿瘤细胞接种后第5天，将左聚糖和环磷酰胺（CY）联合治疗瘤内注射到C57B1小鼠的Lewis肺癌肿瘤中。虽然在当天单独使用左聚糖没有效果，单独使用CY仅导致肿瘤暂时消退，但CY-左聚糖联合治疗导致60%的治愈率。在CY之前给予左聚糖几乎与在第5天同时给予两种药物一样有效。CY治疗后延迟给予左聚糖会降低治疗效果。得出的结论是，相对于肿瘤细胞接种的时间以及药物给药顺序，决定了治疗效果的程度。在肿瘤化学免疫治疗中，最终效果可能不仅归因于每种药物本身的抗肿瘤作用，还归因于这两种药物对免疫系统有影响这一事实。由于免疫反应可能在肿瘤发展过程中发生变化，免疫调节剂给药时间的影响，当然还有两种免疫调节剂给药时间的影响，可能至关重要。
