Falini B, Flenghi L, Fedeli L, Broe M K, Bonino C, Stein H, Dürkop H, Bigerna B, Barbabietola G, Venturi S
Institute of Haematology, University of Perugia, Italy.
Br J Haematol. 1992 Sep;82(1):38-45. doi: 10.1111/j.1365-2141.1992.tb04591.x.
The ability of the Ber-H2 (CD30) monoclonal antibody (mAb) to target in vivo Hodgkin (H) and Reed-Sternberg (R-S) cells was investigated in six patients with advanced Hodgkin's disease (HD). The patients were injected with scaled-up quantities of 'cold' Ber-H2 mixed-up to a small dose of 131I-labelled Ber-H2, and in vivo binding of the antibody to H and R-S cells was assessed by immunohistological analysis of tumour biopsies and immunoscintigraphy. Only 50% of tumour sites were imaged at scintigraphy by the 131I-labelled Ber-H2. In contrast, immunohistological studies on tissue biopsies, taken 24-72 h following the mAb injection, showed that H and R-S cells in all tumour sites, including those that were not imaged by immunoscintigraphy, were specifically and strongly labelled in vivo by the injected Ber-H2, at a dose as low as 30-50 mg of antibody. In vivo binding of a single dose of Ber-H2 mAb to H and R-S cells did not result in any anti-tumour effect. The excellent in vivo targeting of H and R-S cells with the Ber-H2 mAb may have been the result of multiple favourable factors, including: (a) the restricted expression of the CD30 antigen in normal human tissues; (b) the low level of soluble CD30 in the serum of our patients; and (c) the high affinity of the Ber-H2 mAb for the CD30 molecule. The immunohistological results presented in this study provide a strong argument for using the Ber-H2 mAb as a carrier for delivering cytotoxic agents (isotopes or toxins) to neoplastic cells of HD refractory to conventional therapy.
在6例晚期霍奇金病（HD）患者中，研究了Ber-H2（CD30）单克隆抗体（mAb）在体内靶向霍奇金（H）细胞和里德-斯腾伯格（R-S）细胞的能力。给患者注射了放大剂量的“冷”Ber-H2，并混入小剂量的131I标记的Ber-H2，通过肿瘤活检的免疫组织学分析和免疫闪烁显像评估抗体在体内与H细胞和R-S细胞的结合情况。131I标记的Ber-H2在闪烁显像中仅使50%的肿瘤部位显影。相比之下，在注射mAb后24 - 72小时采集的组织活检的免疫组织学研究表明，所有肿瘤部位的H细胞和R-S细胞，包括那些未通过免疫闪烁显像显影的部位，在体内都被注射的Ber-H2特异性且强烈地标记，抗体剂量低至30 - 50毫克。单剂量的Ber-H2 mAb在体内与H细胞和R-S细胞的结合未产生任何抗肿瘤作用。Ber-H2 mAb对H细胞和R-S细胞出色的体内靶向作用可能是多种有利因素的结果，包括：（a）CD30抗原在正常人体组织中的表达受限；（b）我们患者血清中可溶性CD30水平较低；（c）Ber-H2 mAb对CD30分子的高亲和力。本研究中呈现的免疫组织学结果为将Ber-H2 mAb用作载体，向常规治疗难治的HD肿瘤细胞递送细胞毒性剂（同位素或毒素）提供了有力依据。
