Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
Blood. 2010 Jun 10;115(23):4778-86. doi: 10.1182/blood-2009-12-257386. Epub 2010 Feb 24.
Antibody-mediated cell depletion therapy has proven to provide significant clinical benefit in treatment of lymphomas and leukemias, driving the development of improved therapies with novel mechanisms of cell killing. A current clinical target for B-cell lymphoma is CD22, a B-cell-specific member of the sialic acid binding Ig-like lectin (siglec) family that recognizes alpha2-6-linked sialylated glycans as ligands. Here, we describe a novel approach for targeting B lymphoma cells with doxorubicin-loaded liposomal nanoparticles displaying high-affinity glycan ligands of CD22. The targeted liposomes are actively bound and endocytosed by CD22 on B cells, and significantly extend life in a xenograft model of human B-cell lymphoma. Moreover, they bind and kill malignant B cells from peripheral blood samples obtained from patients with hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia. The results demonstrate the potential for using a carbohydrate recognition-based approach for efficiently targeting B cells in vivo that can offer improved treatment options for patients with B-cell malignancies.
抗体介导的细胞耗竭疗法已被证明在治疗淋巴瘤和白血病方面具有显著的临床益处，推动了具有新型细胞杀伤机制的改良疗法的发展。目前，B 细胞淋巴瘤的临床靶点是 CD22，这是唾液酸结合免疫球蛋白样凝集素（siglec）家族中一种 B 细胞特异性成员，可识别作为配体的α2-6 连接的唾液酸化糖。在这里，我们描述了一种使用载有多柔比星的脂质体纳米颗粒靶向 B 淋巴瘤细胞的新方法，这些纳米颗粒展示了 CD22 的高亲和力糖配体。靶向脂质体被 B 细胞上的 CD22 主动结合和内吞，并在人 B 细胞淋巴瘤的异种移植模型中显著延长了生命。此外，它们还能结合并杀死来自毛细胞白血病、边缘区淋巴瘤和慢性淋巴细胞白血病患者外周血样本中的恶性 B 细胞。结果表明，基于碳水化合物识别的方法具有在体内有效靶向 B 细胞的潜力，可为 B 细胞恶性肿瘤患者提供更好的治疗选择。
