Monoclonal antibodies against IREM-1: potential for targeted therapy of AML View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-09

AUTHORS

W Korver, X Zhao, S Singh, C Pardoux, J Zhao, M L Guzman, S Sen, S Yonkovich, S Liu, X Zhan, N Tomasevic, C Zhou, D Gros, C T Jordan, J Gotlib, E D Hsi, A Abo

ABSTRACT

IREM-1 is an inhibitory cell surface receptor with an unknown function and is expressed on myeloid cell lineages, including cell lines derived from acute myeloid leukemia (AML) patients. We have generated a series of monoclonal antibodies (mAbs) against the extracellular domain of IREM-1 and further assessed its expression in normal and AML cells. IREM-1 was restricted to cells from myeloid origin and extensive expression analysis in primary cells obtained from AML patients showed IREM-1 expression in leukemic blasts of 72% (39/54) of samples. We therefore searched for specific IREM-1 mAbs with activity in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Lead mAbs against IREM-1 showed specific cytotoxic activity against a variety of AML-derived cell lines and freshly isolated blasts from AML patients. Internalization of mAbs upon IREM-1 binding was also shown. In vivo anticancer activity of lead mAbs was observed in an established HL-60 xenograft model with a tumor growth delay of up to 40% and in a model using primary human AML cells, where treatment with anti-IREM-1 mAb resulted in a significant reduction of engrafted human cells. These results demonstrate IREM-1 as a potential novel target for immunotherapy of AML. More... »

PAGES

1587

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2009.99

DOI

http://dx.doi.org/10.1038/leu.2009.99

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19440216


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