The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent mannerReport as inadecuate




The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent manner - Download this document for free, or read online. Document in PDF available to download.

Journal of Hematology and Oncology

, 4:49

First Online: 01 December 2011Received: 01 November 2011Accepted: 01 December 2011

Abstract

Most non-Hodgkin-s lymphomas NHL initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma MCL. Bortezomib exerts its activity in part through the generation of reactive oxygen species ROS and also by the induction of apoptosis.

We previously validated CD22 as a potential target in treating NHL and have shown that the anti-CD22 ligand blocking antibody, HB22.7, has significant independent lymphomacidal properties in NHL xenograft models. We sought to determine whether or not these agents would work synergistically to enhance cytotoxicity. Our results indicate that treatment of NHL cell lines with HB22.7 six hours prior to bortezomib significantly diminished cell viability. These effects were not seen when the agents were administered alone or when bortezomib was administered prior to HB22.7. Additionally, HB22.7 treatment prior to bortezomib increased apoptosis in part through enhanced ROS generation. Finally, in a mouse xenograft model, administration of HB22.7 followed 24 hours later by bortezomib resulted in 23% smaller tumor volumes and 20% enhanced survival compared to treatment with the reverse sequence. Despite the increased efficacy of HB22.7 treatment followed by bortezomib, there was no corresponding decrease in peripheral blood cell counts, indicating no increase in toxicity. Our results suggest that pre-treatment with HB22.7 increases bortezomib cytotoxicity, in part through increased reactive oxygen species and apoptosis, and that this sequential treatment combination has robust efficacy in vivo.

KeywordsHB22.7 CD22 bortezomib Velcade proteasome inhibition Non-Hodgkin-s lymphoma reactive oxygen species apoptosis mantle cell lymphoma AbbreviationsNHLnon-Hodgkin-s lymphoma

mAbmonoclonal antibody

ROSreactive oxygen species

MCLmantle cell lymphoma

FLfollicular lymphoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-8722-4-49 contains supplementary material, which is available to authorized users.

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