Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies.
Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies.
复制标题
使用 131I 标记的抗 T 细胞抗体对小鼠淋巴瘤进行实验性放射免疫治疗。
作者：
C. Badger;K A Krohn;Howard M. Shulman;Nancy Flournoy;Irwin D. Bernstein
我们以前已经证明，131 I标记的抗Thy-1.1分化抗原的抗体可以治愈携带AKR/J（Thy-1.1+）SL 2 T细胞淋巴瘤的AKR/Cum（Thy-1.2+）小鼠。在本研究中，我们将这些研究扩展到AKR/J小鼠中的SL 2淋巴瘤的治疗，其中131 I-抗标记的Thy-1.1抗体与肿瘤和正常T淋巴细胞反应。通过与脾细胞结合（t1/2小于3 h），单次25 μ g 131 I标记的抗Thy-1.1抗体推注从血清中快速清除，输注后24 h肿瘤中仅存在低浓度（小于2%注射剂量/g）。0.5-5.0 mg剂量的抗体使脾脏中的细胞饱和，但仅略微增加肿瘤中抗体的比例。相比之下，在131 I标记的抗体之前24小时用1.0 mg未标记的抗Thy-1.1抗体预处理小鼠，导致在输注放射性标记的抗体后24小时肿瘤浓度为9.7%注射剂量/g。使用后一种方案，生物分布接近于在AKR/Cum小鼠中观察到的生物分布，并且1，000 μ Ci的输注将导致向肿瘤递送16戈伊。具有建立的皮下注射的AKR/J小鼠的治疗在后一种方案中给予1，500 μ Ci的131 I-抗-Thy-1.1抗体的淋巴瘤结节导致70%的动物的结节完全消退，并具有更大的抗肿瘤效果（27%完全消退，P小于0.001），而750 μ Ci的131 I标记的无关抗体，该剂量将向正常器官提供等效的辐射（肝、肾和肺）。抗Thy-1.1抗体的抗肿瘤作用仅略大于131 I标记对照抗体的等效μ Ci剂量（1，500 μ Ci）（42%完全回归，P = 0.12）。两种抗体均具有骨髓毒性，所有接受1，500 μ Ci治疗的动物均死于骨髓发育不全。这些研究表明，放射性标记的分化抗原的抗体可能是有用的治疗，尽管结合正常细胞群，但治愈性治疗可能需要输注未照射的骨髓。
We have shown previously that 131I-labeled antibodies against the Thy-1.1 differentiation antigen can cure AKR/Cum (Thy-1.2+) mice bearing AKR/J (Thy-1.1+) SL2 T-cell lymphoma. In the present study we have extended these studies to the therapy of SL2 lymphoma in AKR/J mice, where 131I-anti-labeled Thy-1.1 antibodies react with both tumor and normal T-lymphocytes. A single 25-micrograms bolus of 131I-labeled anti-Thy-1.1 antibody was rapidly cleared from serum by binding to spleen cells (t1/2 less than 3 h) and only low concentrations (less than 2% injected dose/g) were present in tumor 24 h after infusion. Doses of 0.5-5.0 mg antibody saturated cells in the spleen but only slightly increased the proportion of antibody in tumor. In contrast, pretreatment of mice with 1.0 mg of unlabeled anti-Thy-1.1 antibody 24 h prior to 131I-labeled antibody resulted in a tumor concentration of 9.7% injected dose/g 24 h after infusion of the radiolabeled antibody. With this latter regimen, biodistribution approximated that seen in AKR/Cum mice, and infusion of 1,000 mu Ci would result in delivery of 16 Gy to tumor. Therapy of AKR/J mice bearing established s.c. lymphoma nodules with 1,500 mu Ci of 131I-anti-Thy-1.1 antibody given in this latter regimen resulted in complete regression of the nodule in 70% of animals and had a greater antitumor effect (27% complete regression, P less than 0.001) than 750 mu Ci of 131I-labeled irrelevant antibody, a dose that would deliver equivalent radiation to normal organs (liver, kidney, and lung). The anti-Thy-1.1 antibody had only a slightly greater antitumor effect than an equivalent mu Ci dose (1,500 mu Ci) of 131I-labeled control antibody (42% complete regression, P = 0.12). Both antibodies were marrow toxic and all animals treated with 1,500 mu Ci died of marrow aplasia. These studies suggest that radiolabeled antibodies against differentiation antigens may be useful for therapy in spite of binding to normal cell populations but curative therapy may require infusion of unirradiated bone marrow.
肝癌中 131I 标记抗铁蛋白的剂量测定：肿瘤和肝脏中的特定活性。
DOI：
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发表时间：
1983
期刊：
Cancer treatment reports
影响因子：
--
作者：
Leichner,PK;Klein,JL;Siegelman,SS;Ettinger,DS;Order,SE
通讯作者：
Order,SE
用抗 Thy-1 抗原的单克隆抗体治疗 AKR 小鼠淋巴细胞的改变。
影响因子：
6.2
作者：
Tam,MR;Bernstein,ID;Nowinski,RC
通讯作者：
Nowinski,RC
影响因子：
15.9
作者：
LARSON, SM;CARRASQUILLO, JA;HELLSTROM, I
通讯作者：
HELLSTROM, I