Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin's lymphoma

被引:15
作者
Kato, Jason [1 ]
O'Donnell, Robert T. [1 ,2 ]
Abuhay, Mastewal [1 ]
Tuscano, Joseph M. [1 ,2 ]
机构
[1] Univ Calif Davis, Davis Med Ctr, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA 95817 USA
[2] No Calif Vet Healthcare Syst, Martinez, CA USA
关键词
CD22; HB22.7; non-Hodgkin's lymphoma; antibody drug conjugate; saporin; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; ANTI-CD22; MONOCLONAL-ANTIBODY; IN-VITRO; PHASE-I; CYTOTOXIC ACTIVITY; RECEPTOR; CELLS; CD22; IMMUNOCONJUGATE; COMBINATION;
D O I
10.4161/onci.21815
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1469 / 1475
页数:7
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