Effect of interleukin-2 on biodistribution of monoclonal antibody in tumor and normal tissues in mice bearing SL-2 thymoma.
Effect of interleukin-2 on biodistribution of monoclonal antibody in tumor and normal tissues in mice bearing SL-2 thymoma.
复制标题
IL-2对SL-2胸腺瘤小鼠肿瘤和正常组织中单克隆抗体生物分布的影响。
DOI：
10.1093/jnci/84.2.109
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Bernstein,ID
中科院分区：
文献类型：
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作者：
Schultz,KR;Badger,CC;Dombi,GW;Greenberg,PD;Bernstein,ID
背景：我们的实验室先前证明，用肿瘤特异性、放射性标记的抗thy 1小鼠单克隆抗体（MAb）治疗小鼠可以根除t细胞淋巴瘤肿块，但所需剂量对正常器官是有毒的。与正常组织相比，提高肿瘤组织中单克隆抗体浓度的方法可能会克服这个问题。白蛋白外渗表明，白细胞介素-2 （IL-2）可增加毛细血管通透性。目的：本研究的目的是确定单抗在肿瘤部位外渗增加是否可能导致与肿瘤抗原的选择性结合，增加放射标记单抗在肿瘤部位的定位。方法：我们研究了IL-2对1A14单抗（抗th1.1）在正常AKR/Cum （th1.2 +）小鼠和携带SL-2自发性t细胞淋巴瘤（th1.1 +）的AKR/Cum小鼠体内生物分布的影响，并与白蛋白在正常小鼠体内的生物分布和非反应性G3G6单抗在携带肿瘤小鼠体内的生物分布进行了比较。IL-2以0、25000、50000、100000、200000 U的剂量通过尾静脉滴注，每天2次，共7次，持续3.5天。小鼠注射含有1A14 MAb （250 μCi/lOO）的混合物。白蛋白或G3G6 MAb （145 μCi/100）。最后一次IL-2给药后12小时，总体积为200 μL。结果：在正常小鼠中，IL-2引起脾脏、肝脏、肺和淋巴结中放射标记单克隆抗体和白蛋白的剂量依赖性增加，但对大脑没有影响。在荷瘤小鼠中，IL-2在接受注射72小时后导致肿瘤中单克隆抗体水平升高，在每天两次接受10万或20万U IL-2预处理的小鼠中，每克肿瘤的注射剂量分别为17.5%和24.3%，持续3.5天，而对照组为13.4%。在il -2处理的小鼠中，肿瘤中的MAb水平高于关键正常器官；注射后24小时肿瘤与肺的差异以及注射后48小时和72小时肿瘤与肝脏的差异具有统计学意义。结论：这些结果表明，与正常组织相比，IL-2预处理可能导致肿瘤特异性单抗在肿瘤部位的分布增强，从而提高放射标记单抗的治疗效果。[J].中华肿瘤杂志，2004,27(4):391 - 391。
Background: Our laboratory demonstrated previously that treatment with a tumor-specific, radiolabeled anti-Thy 1 murine monoclonal antibody (MAb) in mice can eradicate a T-cell lymphoma mass, but the doses required were toxic to normal organs. Approaches to increase MAb concentration in tumor tissue versus normal tissue may overcome this problem. Interleukin-2 (IL-2) has been shown to increase capillary permeability, as indicated by extravasation of albumin.Purpose: The purpose of this study was to determine whether increased extravasation of MAb at the tumor site might result in selective binding to tumor antigen, increasing localization of radiolabeled MAb at the tumor site.Methods: We studied the effect of IL-2 on biodistribution of 1A14 MAb (anti-Thy 1.1) in normal AKR/Cum (Thy 1.2+) mice and in AKR/Cum mice bearing SL-2, a spontaneous T-cell lymphoma (Thy 1.1+), compared with biodistribution of albumin in normal mice and biodistribution of the nonreactive G3G6 MAb in tumor-bearing mice. IL-2 was given intravenously in the tail vein in doses of 0, 25000, 50000, 100000, or 200000 U twice a day for a total of seven doses over 3.5 days. Mice received injections of a mixture of 1A14 MAb (250 μCi/lOO.μg) and albumin or G3G6 MAb (145 μCi/100.μg) in a total volume of 200 μL at 12 hours after the last IL-2 dose.Results: In normal mice, IL-2 caused a dose-dependent increase of both radiolabeled MAb and albumin in the spleen, liver, lung, and lymph node, but it spared the brain. In tumor- bearing mice, IL-2 resulted in higher levels of MAb in the tumors 72 hours after receiving injections, with 17.5% and 24.3% of the injected dose per gram of tumor present in the mice pretreated with 100 000 or 200 000 U of IL-2 twice a day for 3.5 days, compared with 13.4% in the controls. In IL-2-treated mice, levels of MAb were greater in the tumors than in critical normal organs; the differences were statistically significant for tumors versus lungs at 24 hours after injection and for tumors versus livers at 48 hours and 72 hours after injection.Conclusions: These results suggest that pretreatment with IL-2 may lead to enhanced distribution of tumor-specific MAb to the tumor site, compared with normal tissues, thus increasing therapeutic efficacy of radiolabeled MAb. [J Natl Cancer Inst 84:109-113, 1992].