Maas R A, Dullens H F, De Jong W H, Den Otter W
Department of Pathology, University Hospital Utrecht, The Netherlands.
Cancer Res. 1989 Dec 15;49(24 Pt 1):7037-40.
Successful immunotherapy with recombinant interleukin 2 (rIL-2) of mice bearing a large burden of lymphokine-activated killer-resistant disseminated SL2 lymphoma is described. When mice were challenged i.p. with 2 x 10(4) SL2 cells on day 0 and treated with daily i.p. injections of 5,000 units rIL-2 on days 3-7, no therapeutic effect was observed. However after treatment with daily IL-2 injections on day 10-14, 25% of the mice survived. Ten days after this tumor challenge more than 10(8) SL2 cells were present growing as ascitic tumor. On day 10, SL2 cells were also present as solid tumor in the greater omentum and as metastases in lungs and liver. Surviving mice were able to reject a second challenge with SL2 cells given on day 60. A second challenge with P815, another DBA/2 tumor, resulted in death of the mice due to tumor development. This finding is of particular importance as the SL2 cells are resistant to lymphokine-activated killer activity. Thus local (i.p.) injection of low dose rIL-2 can cause the systemic rejection of advanced and metastasized cancer. Our data indicate that IL-2 can strongly enhance a specific immune reaction against tumor cells.
本文描述了对携带大量对淋巴因子激活的杀伤细胞具有抗性的播散性SL2淋巴瘤的小鼠，使用重组白细胞介素2（rIL-2）进行成功免疫治疗的情况。在第0天给小鼠腹腔注射2×10⁴个SL2细胞，并在第3至7天每天腹腔注射5000单位rIL-2进行治疗时，未观察到治疗效果。然而，在第10至14天每天注射IL-2进行治疗后，25%的小鼠存活下来。在这种肿瘤攻击10天后，超过10⁸个SL2细胞以腹水瘤的形式生长。在第10天，SL2细胞也以实体瘤的形式存在于大网膜中，并以转移瘤的形式存在于肺和肝脏中。存活的小鼠能够排斥在第60天给予的第二次SL2细胞攻击。用另一种DBA/2肿瘤P815进行第二次攻击，导致小鼠因肿瘤发展而死亡。这一发现尤为重要，因为SL2细胞对淋巴因子激活的杀伤细胞活性具有抗性。因此，局部（腹腔）注射低剂量rIL-2可导致对晚期和转移性癌症的全身排斥。我们的数据表明，IL-2可强烈增强针对肿瘤细胞的特异性免疫反应。
