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- Title
Monoclonal antibodies against IREM-1: potential for targeted therapy of AML.
- Authors
Korver, W; Zhao, X; Singh, S; Pardoux, C; Zhao, J; Guzman, M L; Sen, S; Yonkovich, S; Liu, S; Zhan, X; Tomasevic, N; Zhou, C; Gros, D; Jordan, C T; Gotlib, J; Hsi, E D; Abo, A
- 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.
- Publication
Leukemia, 2009, Vol 23, Issue 9, p1587
- ISSN
1476-5551
- Publication type
Journal Article
- DOI
10.1038/leu.2009.99