Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)
Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)
复制标题
DOI：
10.1007/s10637-009-9243-7
复制
发表时间：
2010-06-01
影响因子：
3.4
通讯作者：
Tuscano, Joseph M.
中科院分区：
文献类型：
--
作者：
O'Donnell, Robert T.;Martin, Shiloh M.;Tuscano, Joseph M.
非霍奇金淋巴瘤（NHL）是美国癌症死亡的第六大常见原因。大多数NHL最初对化疗反应良好，但复发很常见，并且由于化疗药物的毒性，治疗往往受到限制。聚乙二醇化脂质体多柔比星（PLD，Ben Venue Laboratories，Inc）a产生的骨髓毒性低于非脂质体（NL）多柔比星。为了进一步增强疗效和NHL靶向并降低毒性，我们将抗CD 22单克隆抗体（HB22.7）缀合至PLD表面，从而产生CD 22靶向免疫脂质体PLD（IL-PLD）。HB22.7成功地与PLD偶联，通过免疫荧光染色评估，所得IL-PLD表现出与表达CD 22的细胞的特异性结合。IL-PLD在CD 22阳性细胞系中表现出比PLD更大的细胞毒性，但不增加对CD 22阴性细胞的杀伤。IL-PLD对CD_（22）+细胞的IC_（50）比PLD低3.1 ~ 5.4倍，而对CD_（22）-细胞的IC_（50）与PLD相当。此外，IL-PLD在洗涤后保持与CD 22+细胞结合并继续发挥细胞毒性作用，而PLD和NL-阿霉素可以容易地从这些细胞中洗涤出来。
Non-Hodgkin's lymphoma (NHL) is the sixth most common cause of cancer deaths in the U.S. Most NHLs initially respond well to chemotherapy, but relapse is common and treatment is often limited due to the toxicity of chemotherapeutic agents. Pegylated-liposomal doxorubicin (PLD, Ben Venue Laboratories, Inc), a produces less myelotoxicity than non-liposomal (NL) doxorubicin. To further enhance efficacy and NHL targeting and to decrease toxicity, we conjugated an anti-CD22 monoclonal antibody (HB22.7) to the surface of PLD, thereby creating CD22-targeted immunoliposomal PLD (IL-PLD). HB22.7 was successfully conjugated to PLD and the resulting IL-PLD exhibits specific binding to CD22-expressing cells as assessed by immunofluorescence staining. IL-PLD exhibits more cytotoxicity than PLD in CD22 positive cell lines but does not increase killing of CD22 negative cells. The IC50 of IL-PLD is 3.1 to 5.4 times lower than that of PLD in CD22+ cell lines while the IC50 of IL-PLD is equal to that of PLD in CD22- cells. Furthermore, IL-PLD remained bound to the CD22+ cells after washing and continued to exert cytotoxic effects, while PLD and NL- doxorubicin could easily be washed from these cells.