Maekawa R, Matsumoto M, Kitagawa T, Harada M, Sato K
Cancer Immunol Immunother. 1986;23(1):25-30. doi: 10.1007/BF00205551.
The present study deals with the effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563. Administration of R-IL2 (5 X 10(4) J.U./mouse per day) s. c. starting 1 day after X5563 inoculation i.d. had a marginal effect on the growth of X5563, and all the mice repeatedly given R-IL2 from day 1 to day 17 died. However, daily administration of R-IL2 starting 7 days after the tumor inoculation was highly effective and significantly lengthened survival time compared with the control mice injected with vehicle alone. About 50% of the treated mice were completely cured, and survived for more than a month after the therapy ceased. In a representative experiment, where the growth of X5563 was slow because of the small number of inoculated tumor cells, all the mice (n = 6) given R-IL2 from day 11 to day 23 showed complete cure of the established X5563 solid tumor. These mice showed in vivo protective immunity and in vitro cytotoxic T cell responses to X5563 tumor antigens. Histologically, a large number of macrophages and lymphocytes had infiltrated the area around the necrotic X5563 tumor mass in the mice which had received R-IL2 therapy. These results suggest that repeated injections of R-IL2 at the local site after tumor development can augment antitumor immunological responses and subsequently induce tumor regression.
本研究探讨重组白细胞介素2(R-IL2)对小鼠骨髓瘤X5563体内生长的影响。在X5563皮下接种后1天开始皮下注射R-IL2(5×10⁴ J.U./只小鼠/天),对X5563的生长影响甚微,且所有从第1天至第17天反复给予R-IL2的小鼠均死亡。然而,在肿瘤接种7天后开始每日给予R-IL2则非常有效,与仅注射赋形剂的对照小鼠相比,显著延长了存活时间。约50%的治疗小鼠完全治愈,在治疗停止后存活超过1个月。在一个代表性实验中,由于接种的肿瘤细胞数量少,X5563生长缓慢,所有从第11天至第23天给予R-IL2的小鼠(n = 6)已建立的X5563实体瘤均完全治愈。这些小鼠表现出对X5563肿瘤抗原的体内保护性免疫和体外细胞毒性T细胞反应。组织学上,在接受R-IL2治疗的小鼠中,大量巨噬细胞和淋巴细胞浸润到坏死的X5563肿瘤块周围区域。这些结果表明,肿瘤发生后在局部反复注射R-IL2可增强抗肿瘤免疫反应,随后诱导肿瘤消退。