Radiotherapy of CD19 expressing Daudi tumors in nude mice with Yttrium-90-labeled anti-CD19 antibody.
Radiotherapy of CD19 expressing Daudi tumors in nude mice with Yttrium-90-labeled anti-CD19 antibody.
复制标题
用钇90标记的抗CD19抗体对裸鼠中表达CD19的Daudi肿瘤进行放射治疗。
DOI：
10.1089/108497804773391630
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发表时间：
2004
影响因子：
3.4
通讯作者：
Kersey,JohnH
中科院分区：
文献类型：
--
作者：
Vallera,DanielA;Elson,Michael;Brechbiel,MartinW;Dusenbery,KathrynE;Burns,LindaJ;Jaszcz,WaclawB;Ramsay,NormaK;Panoskaltsis-Mortar,Angela;Kuroki,DavidW;Wagner,JohnE;Vitetta,EllenS;Kersey,JohnH
进行研究以确定使用两种不同的抗CD 19单克隆抗体将高能β粒子发射同位素90 Y递送至生长的B细胞淋巴瘤的适合性。 作为无胸腺裸鼠的侧腹肿瘤。抗体BU 12和HD 37均为IgG 1亚类，识别CD 19，CD 19是一种内化B系特异性膜糖蛋白，是IG超基因家族的成员。 使用高度稳定的螯合物1B 4 M-MX-DTPA容易地用90 Y标记抗体。放射免疫偶联物选择性结合表达CD 19的B细胞系Daudi，但不结合CD 19 阴性对照细胞。与对照非结合抗体相比，90 Y抗CD 19与裸鼠中生长的Daudi肿瘤的结合显著更多（p = 0.001）。生物分布数据与 抗肿瘤作用。抗肿瘤活性是剂量依赖性的，并且在接受约300 uCi的单次剂量的小鼠中观察到最佳结果。抗-CD 19抗体具有显著更好的 抗肿瘤活性，并且大多数小鼠存活超过119天，没有肿瘤迹象（p < 0.003）。组织学研究显示无明显损伤 肾脏肝脏或小肠由于放射性标记的抗CD 19抗体可用于选择性地向淋巴造血组织递送辐射，因此这些数据支持使用90 Y 抗CD 19抗体治疗B细胞恶性肿瘤。
Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of90Y anti-CD19 antibodies in treating B-cell malignancies.