Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
Leuk Lymphoma. 2012 Feb;53(2):208-10. doi: 10.3109/10428194.2011.604755. Epub 2011 Aug 24.
CD22 is a member of the siglec (sialic acid-binding immunoglobulin-like lectin) family expressed on B cells that recognizes glycans of glycoproteins as ligands. Because siglecs exhibit restricted expression on one or a few leukocyte cell types, they have gained attention as attractive targets for cell-directed therapies. Several antibody-based therapies targeting CD22 (Siglec-2) are currently in clinical trials for the treatment of hairy cell leukemia and other B cell lymphomas. As an alternative to antibodies we have developed liposomal nanoparticles decorated with glycan ligands of CD22 that selectively target B cells. Because CD22 is an endocytic receptor, ligand-decorated liposomes are bound by CD22 and rapidly internalized by the cell. When loaded with a toxic cargo such as doxorubicin, they are efficacious in prolonging life in a Daudi B cell lymphoma model. These B cell targeted nanoparticles have been demonstrated to bind and kill malignant B cells from patients with hairy cell leukemia, marginal zone lymphoma and chronic lymphocytic leukemia. The results demonstrate the potential of using CD22 ligand-targeted liposomal nanoparticles as an alternative approach for the treatment of B cell malignancies.
CD22 是 B 细胞上表达的 siglec（唾液酸结合免疫球蛋白样凝集素）家族的成员，它以糖蛋白的糖基作为配体识别。由于 siglecs 在一种或几种白细胞上呈限制表达，因此它们作为细胞定向治疗的有吸引力的靶点而备受关注。目前有几种针对 CD22（Siglec-2）的抗体靶向治疗方法正在临床试验中，用于治疗毛细胞白血病和其他 B 细胞淋巴瘤。作为抗体的替代物，我们开发了带有 CD22 糖基配体的脂质体纳米颗粒，这些纳米颗粒能够特异性地靶向 B 细胞。由于 CD22 是一种内吞受体，配体修饰的脂质体通过 CD22 结合并被细胞迅速内化。当装载上阿霉素等有毒货物时，它们在 Daudi B 细胞淋巴瘤模型中能有效延长生命。这些靶向 B 细胞的纳米颗粒已被证明能与来自毛细胞白血病、边缘区淋巴瘤和慢性淋巴细胞白血病患者的恶性 B 细胞结合并杀死它们。这些结果表明，使用 CD22 配体靶向脂质体纳米颗粒作为治疗 B 细胞恶性肿瘤的替代方法具有潜力。
