An antibody inhibitor of the LMO2-protein complex blocks its normal and tumorigenic functions.

Journal article

The LIM-domain protein LMO2 is a T-cell oncogenic protein first recognized by gene activation through chromosomal translocations, but it is also responsible for leukaemias arising as secondary, adverse effects in an X-SCID gene therapy trial. There are no specific reagents currently available to analyse the LMO2 multiprotein complex or to combat LMO2-dependent leukaemias. Accordingly, we have isolated an anti-LMO2 single chain Fv antibody fragment to determine if intracellular interference with LMO2-protein complexes can avert LMO2-dependent functions in normal and cancer settings. The anti-LMO2 single chain Fv, obtained using Intracellular Antibody Capture (IAC) technology, is specific for LMO2 among the LIM-only protein family and binds LMO2 through the third and fourth LIM fingers. Using vector-mediated expression of anti-LMO2 scFv, we show inhibition of Lmo2-dependent erythropoiesis but not endothelial development. We also demonstrate inhibition of Lmo2-dependent leukaemia in a mouse T-cell tumourigenesis transplantation assay with retroviral-mediated expression of anti-LMO2 scFv. Our studies establish that interference with the LMO2 multiprotein complex inhibits both normal and tumourigenic roles. The antibody fragment is a tool for dissecting LMO2 function in haematopoiesis and leukaemia and is a lead for development of therapeutics against LMO2-dependent T-ALL.

Authors: Nam, C; Lobato, M; Appert, A; Drynan, L; Tanaka, T

• Journal: Oncogene
• Volume: 27
• Issue: 36
• Pages: 4962-4968
• Publication date: 2008-08-01
• DOI: 10.1038/onc.2008.130
• EISSN: 1476-5594
• ISSN: 0950-9232
• Language: English
• Keywords: Mice; Antibodies; Cricetinae; Metalloproteins; LIM Domain Proteins; DNA-Binding Proteins; Leukemia, T-Cell; Adaptor Proteins, Signal Transducing; Animals; Green Fluorescent Proteins; CHO Cells; Cricetulus