Meredith Ruby F, Buchsbaum Donald J
Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Int J Radiat Oncol Biol Phys. 2006;66(2 Suppl):S57-9. doi: 10.1016/j.ijrobp.2006.04.058.
This brief review covers the concept of pretargeted radioimmunotherapy and summarize the results obtained in preclinical animal models and initial phase I clinical trials. Reagents studied have been a bifunctional antibody prepared by crosslinking Fab' fragments from two antibodies with different specificity, one binding the target antigen expressed on tumors and the other binding a radiolabeled peptide. The alternative system is a conjugate of streptavidin linked to the pretargeting agent and radiolabeled biotin. After reaching optimal tumor targeting of the pretargeting agent, a synthetic mono-biotin poly N-acetyl-galactosamine compound was used to clear unbound targeting agent from the circulation before the injection of radiolabeled biotin. Promising therapeutic responses were obtained in various tumor xenograft models in athymic nude mice. A phase I study of an anti-CD20/streptavidin pretargeting agent and 15 mCi/m(2)(90)Y-biotin produced objective responses with minimal toxicity among lymphoma patients, with an average tumor-to-whole-body radiation dose ratio of 49. Pretargeting radioimmunotherapy approaches have shown higher tumor-to-whole-body ratios than that usually obtained with one-step radioimmunotherapy.
本简要综述涵盖了预靶向放射免疫疗法的概念，并总结了在临床前动物模型和I期临床试验初期所取得的结果。所研究的试剂包括一种双功能抗体，它通过交联来自两种具有不同特异性的抗体的Fab'片段制备而成，一种抗体结合肿瘤上表达的靶抗原，另一种抗体结合放射性标记的肽。另一种系统是与预靶向剂连接的链霉亲和素和放射性标记生物素的缀合物。在预靶向剂达到最佳肿瘤靶向效果后，在注射放射性标记生物素之前，使用一种合成的单生物素聚N-乙酰半乳糖胺化合物清除循环中未结合的靶向剂。在无胸腺裸鼠的各种肿瘤异种移植模型中获得了有前景的治疗反应。一项关于抗CD20/链霉亲和素预靶向剂和15 mCi/m² (90)Y-生物素的I期研究在淋巴瘤患者中产生了客观反应，且毒性极小，肿瘤与全身辐射剂量平均比值为49。预靶向放射免疫疗法方法显示出比一步法放射免疫疗法通常获得的更高的肿瘤与全身比值。
