Sapra Puja, Allen Theresa M
Department of Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2H7 Canada.
Cancer Res. 2002 Dec 15;62(24):7190-4.
Direct experimental proof has been sought for the hypothesis that liposomal drugs targeted against internalizing epitopes (e.g., CD19) will have higher therapeutic efficacies than those targeted against noninternalizing epitopes (e.g., CD20). Anti-CD19-targeted liposomes were rapidly internalized into human B-lymphoma (Namalwa) cells, whereas those targeted with anti-CD20 were not internalized. Similar in vitro binding and cytotoxicity were observed for anti-CD19-targeted and anti-CD20-targeted liposomal formulations of doxorubicin (DXR). Therapeutic experiments were performed in severe combined immunodeficient mice inoculated i.v. with Namalwa cells. Administration of single i.v. doses of DXR-loaded anti-CD19-targeted liposomes resulted in significantly greater survival times than either DXR-loaded anti-CD20-targeted liposomes or nontargeted liposomes. The therapeutic advantage of targeting internalizing versus noninternalizing epitopes has been directly demonstrated.
针对内化表位（如CD19）的脂质体药物比针对非内化表位（如CD20）的脂质体药物具有更高治疗效果这一假说，人们一直在寻求直接的实验证据。抗CD19靶向脂质体能够迅速内化进入人B淋巴瘤（Namalwa）细胞，而抗CD20靶向脂质体则不会被内化。对于阿霉素（DXR）的抗CD19靶向和抗CD20靶向脂质体制剂，观察到了相似的体外结合和细胞毒性。在通过静脉注射接种Namalwa细胞的严重联合免疫缺陷小鼠中进行了治疗实验。单次静脉注射负载DXR的抗CD19靶向脂质体给药后，其存活时间显著长于负载DXR的抗CD20靶向脂质体或非靶向脂质体。靶向内化表位与非内化表位的治疗优势已得到直接证明。
