Division of Hematology and Oncology; Department of Internal Medicine; University of California, Davis Cancer Center; Sacramento, CA USA.
Oncoimmunology. 2012 Dec 1;1(9):1469-1475. doi: 10.4161/onci.21815.
Antibody drug conjugates (ADCs) can deliver potent drugs to cancer cells by employing the specificity of monoclonal antibodies (mAbs). ADCs have demonstrated significant anticancer activity and, in 2011, brentuximab vedotin has been approved by the FDA for the treatment of Hodgkin's and anaplastic large cell lymphomas. CD22 is an ideal target for ADC against B-cell malignancies because of its lineage-specific expression and rapid internalization upon antibody binding. In this study, we evaluated the anti-CD22 mAb HB22.7 as a vehicle for the targeted delivery of the potent toxin saporin (SAP). In vitro, HB22.7-SAP was cytotoxic against a panel of non-Hodgkin's lymphoma (NHL) cell lines representing the most common types of the disease. Moreover, in a xenograft model of NHL, HB22.7-SAP significantly inhibited the growth of established lesions and completely prevented tumor development when treatment was initiated within 24 h from tumor-cell inoculation. HB22.7-SAP had no significant in vivo toxicity. In conclusion, HB22.7 constitutes a potential platform for CD22-targeted ADCs.
抗体药物偶联物(ADCs)可以通过利用单克隆抗体(mAbs)的特异性将有效药物递送到癌细胞中。ADCs 已显示出显著的抗癌活性,并且在 2011 年,brentuximab vedotin 已被 FDA 批准用于治疗霍奇金淋巴瘤和间变性大细胞淋巴瘤。CD22 是针对 B 细胞恶性肿瘤的 ADC 的理想靶点,因为它在谱系特异性表达,并在抗体结合后迅速内化。在这项研究中,我们评估了抗 CD22 mAb HB22.7 作为靶向递送有效毒素 saporin (SAP) 的载体。体外,HB22.7-SAP 对一系列非霍奇金淋巴瘤(NHL)细胞系具有细胞毒性,这些细胞系代表了该疾病最常见的类型。此外,在 NHL 的异种移植模型中,当在肿瘤细胞接种后 24 小时内开始治疗时,HB22.7-SAP 显著抑制了已建立的病变的生长,并完全阻止了肿瘤的发展。HB22.7-SAP 没有明显的体内毒性。总之,HB22.7 构成了 CD22 靶向 ADC 的潜在平台。