Ozaki S, Kosaka M, Harada M, Nishitani H, Odomi M, Matsumoto T
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Cancer. 1998 Jun 1;82(11):2184-90. doi: 10.1002/(sici)1097-0142(19980601)82:11<2184::aid-cncr13>3.0.co;2-q.
To develop a new immunologic approach to multiple myeloma, the authors generated a monoclonal antibody against a human plasma cell specific antigen, HM1.24. Their previous study showed the antitumor effect of this antibody in severe combined immunodeficiency (SCID) mice bearing human myeloma xenografts. In the current study, the efficacy of anti-HM1.24 immunoglobulin (Ig) G and its F(ab')2 fragment were evaluated for radioimmunologic detection of the myeloma xenografts.
SCID mice bearing subcutaneous RPMI 8226 tumors were injected with 125I-labeled antibodies, and radioactivity in the tumor and normal tissues was measured. Radioimmunoscintigraphy and autoradiography were performed to investigate the distribution of the antibodies.
In comparative biodistribution studies, the maximum tumor localization index of anti-HMl.24 F(ab')2 fragment was significantly higher than that of anti-HM1.24 IgG. Anti-HM1.24 F(ab')2 consistently had higher tumor-to-tissue ratio than anti-HM1.24 IgG and gave distinct tumor images by radioimmunoscintigraphy. Autoradiographic study showed that anti-HM1.24 F(ab')2 penetrated the tumor mass more uniformly than whole IgG antibody.
These results indicate that anti-HM1.24 antibody has the potential to provide a new approach to the immunodetection and immunotherapy of multiple myeloma and related plasma cell dyscrasias.
为开发一种针对多发性骨髓瘤的新免疫方法，作者制备了一种针对人浆细胞特异性抗原HM1.24的单克隆抗体。他们之前的研究显示了该抗体对携带人骨髓瘤异种移植物的严重联合免疫缺陷（SCID）小鼠的抗肿瘤作用。在本研究中，评估了抗HM1.24免疫球蛋白（Ig）G及其F（ab'）2片段对骨髓瘤异种移植物进行放射免疫检测的效果。
给携带皮下RPMI 8226肿瘤的SCID小鼠注射125I标记的抗体，并测量肿瘤和正常组织中的放射性。进行放射免疫闪烁显像和放射自显影以研究抗体的分布。
在比较生物分布研究中，抗HMl.24 F（ab'）2片段的最大肿瘤定位指数显著高于抗HM1.24 IgG。抗HM1.24 F（ab'）2的肿瘤与组织比值始终高于抗HM1.24 IgG，并通过放射免疫闪烁显像给出清晰的肿瘤图像。放射自显影研究表明，抗HM1.24 F（ab'）2比完整的IgG抗体更均匀地穿透肿瘤块。
这些结果表明，抗HM1.24抗体有可能为多发性骨髓瘤及相关浆细胞发育异常的免疫检测和免疫治疗提供一种新方法。
