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

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 anaplas...

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Bibliographic Details
Published in:Oncoimmunology 2012-12, Vol.1 (9), p.1469-1475
Main Authors: Kato, Jason, O'Donnell, Robert T., Abuhay, Mastewal, Tuscano, Joseph M.
Format: Article
Language:English
Subjects:
antibody drug conjugate
Binding
Biology
Bioscience
Calcium
Cancer
CD22
Cell
Cycle
HB22.7
Landes
non-Hodgkin's lymphoma
Organogenesis
Proteins
Research Paper
saporin
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Summary: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.
ISSN:2162-4011
2162-402X
2162-402X
DOI:10.4161/onci.21815