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目的 探讨冷冻治疗附加免疫治疗可能获得更好的抗肿瘤疗效。方法 B16黑素瘤皮下接种 C5 7BL / 6小鼠 ,待肿瘤长至 3mm～ 5 m m时荷瘤鼠分为四组。 1冷冻免疫组 :第 0天 ,用深部冷冻治疗仪治疗荷瘤鼠 1次。冷冻治疗前2天每只小鼠腹腔注射 1mg环磷酰胺 1次 ,肿瘤局部每天注射 IFN -α 5万单位 ,共 2天。从第 0天至第 10天 ,每天给小鼠注射 1万单位 r IL - 2。 2、3、4组分别为冷冻治疗组、免疫治疗组和未治疗对照组。根据肿瘤大小和存活时间评价疗效。用 3H- Td R释放法测定脾细胞的细胞毒活性。结果 肿瘤接种后第 31天 ,仅第 1组肿瘤平均大小与对照组相比有显著差异 (P<0 .0 1)。各组平均存活期依次为 6 8.7、5 5 .3、5 1.6和41天。肿瘤完全缓解率组 1为 43.8% ,组 2为 11.8% ,而其他两组无 1例缓解。组 1治愈小鼠用 B16再次攻击均未产生肿瘤。组 1小鼠脾细胞体外细胞毒实验按效靶比为 5 0∶ 1时 ,对 B16的杀伤率为 42 .1% ,对 EL 4杀伤仅为 3.5 %。结论 用 IFN -α和 r IL - 2免疫治疗协同冷冻治疗可能通过诱发全身性、特异性抗肿瘤免疫反应 ,获得更好的疗效。
OBJECTIVE: To investigate whether cryotherapy for adjuvant immunotherapy may achieve better antitumor efficacy. Methods B16 melanoma was inoculated subcutaneously in C5 7BL / 6 mice. When the tumor grew to 3mm ~ 5m m, the tumor-bearing mice were divided into four groups. 1 frozen immunity group: On the 0th day, deep freezing treatment instrument treatment of tumor-bearing mice 1 times. Two days before freezing treatment, each mouse was given intraperitoneal injection of 1mg cyclophosphamide once a day, and the tumor was locally injected with 50,000 units of IFN-α daily for 2 days. Mice were injected with 10,000 IL-2 per day from day 0 to day 10. Groups 2, 3 and 4 were cryotherapy group, immunotherapy group and untreated control group respectively. Efficacy was assessed based on tumor size and survival time. The cytotoxic activity of spleen cells was determined by 3H-Td R release assay. Results On the 31st day after tumor inoculation, only the mean tumor size in group 1 was significantly different from that in control group (P <0.01). The average survival for each group was 6 8.7, 5.53, 3.5, 1.6 and 41 days. Complete tumor response rate was 43.8% in group 1, 11.8% in group 2, and none in the other two groups. None of the mice in group 1 who were challenged with B16 to attack again developed tumors. In vitro cytotoxicity test of group 1 mouse spleen cells showed that the killing rate of B16 was 42.1% and the killing rate of EL 4 was only 3.5%. Conclusions The synergistic cryotherapy with IFN-α and IL-2 immunotherapy may lead to better efficacy by inducing systemic and specific anti-tumor immune responses.