Everse L A, Renes I B, Jürgenliemk-Schulz I M, Rutgers D H, Bernsen M R, Dullens H F, Den Otter W, Battermann J J
Department of Radiotherapy, Academic Hospital, Utrecht, The Netherlands.
Int J Cancer. 1997 Sep 17;72(6):1003-7. doi: 10.1002/(sici)1097-0215(19970917)72:6<1003::aid-ijc14>3.0.co;2-5.
Tumor recurrence and outgrowth of metastases limit the therapeutical effect of radiotherapy. We have tested whether these problems can be overcome by supplementing radiotherapy with locoregional interleukin-2 (IL-2) treatment. The SL2 lymphoma and the M8013 mammary carcinoma were used. Mice bearing a 10-day-old s.c. tumor were locally irradiated and were treated daily with IL-2 peritumorally for 5 or 10 days. Low-dose IL-2 therapy improved local response (LR) and increased disease-free survival (DFS) in both tumor models following either single-dose irradiation or fractionated irradiation. For example, 93% of SL2-bearing mice treated with single-dose irradiation and 10 days of IL-2 experienced long-term DFS, compared with 17% for irradiation alone (p < 0.0001). Additionally, treatment of one tumor with irradiation +IL-2 led to anti-tumor effects in a second, untreated tumor in 80% of SL2-bearing mice. LR was increased to 100% and DFS to 70% when the second, non-irradiated tumor was also treated with peritumoral IL-2. We conclude that supplementing local radiotherapy with low doses of IL-2 results in increased local tumor control and regression of distant, non-irradiated tumors. This type of radioimmunotherapy is a promising new approach for the clinic.
肿瘤复发和转移灶的生长限制了放射治疗的疗效。我们测试了通过局部注射白细胞介素-2（IL-2）辅助放射治疗是否可以克服这些问题。使用了SL2淋巴瘤和M8013乳腺癌模型。对皮下接种肿瘤10天的小鼠进行局部照射，并在肿瘤周围每天注射IL-2，持续5天或10天。在单剂量照射或分次照射后的两种肿瘤模型中，低剂量IL-2治疗均改善了局部反应（LR）并延长了无病生存期（DFS）。例如，接受单剂量照射并注射10天IL-2的荷SL2肿瘤小鼠中，93%经历了长期DFS，而单纯照射组为17%（p<0.0001）。此外，在80%的荷SL2肿瘤小鼠中，对一个肿瘤进行照射+IL-2治疗会对第二个未治疗的肿瘤产生抗肿瘤作用。当对第二个未照射的肿瘤也进行肿瘤周围IL-2治疗时，LR增加到100%，DFS增加到70%。我们得出结论，低剂量IL-2辅助局部放射治疗可提高局部肿瘤控制率，并使远处未照射肿瘤消退。这种放射免疫治疗是一种有前景的临床新方法。
