BACKGROUND: β2 Integrins (cluster of differentiation-18, CD18) are expressed only by leukocytes and serve as cell surface receptors, being involved both in inside-out and outside-in signalling, and in cell movement. Therefore, they are interesting targets for therapeutic intervention. Phage display-derived inhibitory peptides against αMβ2 integrins (macrophage-1 antigen, Mac-1) have been found to be effective in preventing leukocyte movement in vitro and in vivo but little is known regarding their ability to target leukaemia and lymphoma in vivo. MATERIALS AND METHODS: Athymic nude mice were inoculated with human THP-1 acute monocytic leukemia (AML-M5 variant), U937 diffuse histiocytic lymphoma, and OCI-AML-3 acute-myeloidic leukemia cells, and then treated with Mac-1-inhibiting peptides ADGACILWMDDGWCGAAG (DDGW) or CPCLLGCC fused with green fluorescent protein (LLG-GFP). RESULTS: Mac-1-inhibiting DDGW peptide had no effect on leukemia and lymphoma burden in mice, and LLG-GFP fusion did not home to leukemia cells in vivo. CONCLUSION: Although peptides against Mac-1 are promising drugs and diagnostic tools based on earlier experiments in inflammation they exhibit compromised biological avidity as a therapeutic and diagnostic means for leukaemia and lymphoma.
BACKGROUND: β2 Integrins (cluster of differentiation-18, CD18) are expressed only by leukocytes and serve as cell surface receptors, being involved both in inside-out and outside-in signalling, and in cell movement. Therefore, they are interesting targets for therapeutic intervention. Phage display-derived inhibitory peptides against αMβ2 integrins (macrophage-1 antigen, Mac-1) have been found to be effective in preventing leukocyte movement in vitro and in vivo but little is known regarding their ability to target leukaemia and lymphoma in vivo. MATERIALS AND METHODS: Athymic nude mice were inoculated with human THP-1 acute monocytic leukemia (AML-M5 variant), U937 diffuse histiocytic lymphoma, and OCI-AML-3 acute-myeloidic leukemia cells, and then treated with Mac-1-inhibiting peptides ADGACILWMDDGWCGAAG (DDGW) or CPCLLGCC fused with green fluorescent protein (LLG-GFP). RESULTS:Mac-1-inhibiting DDGW peptide had no effect on leukemia and lymphoma burden in mice, and LLG-GFP fusion did not home to leukemia cells in vivo. CONCLUSION: Although peptides against Mac-1 are promising drugs and diagnostic tools based on earlier experiments in inflammation they exhibit compromised biological avidity as a therapeutic and diagnostic means for leukaemia and lymphoma.
Authors: Juho Suojanen; Niko Lehtonen; Esa Färkkilä; Jarkko Hietanen; Olli Teronen; Timo Sorsa; Jaana Hagström Journal: J Clin Diagn Res Date: 2014-09-20