title: Peptides against Mac-1 do not sufficiently target leukemia or lymphoma in vivo.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Biomedicum Helsinki, P.O. Box 63, Haartmaninkatu 8, FI-00014 University of Helsinki, Finland. juho.suojanen@helsinki.fi.
authors: Juho
authors: J
authors: Suojanen
authors: Justus
authors: J
authors: Reunanen
authors: Tanja-Maria
authors: TM
authors: Ranta
authors: Oula
authors: O
authors: Peñate-Medina
authors: Tuula
authors: T
authors: Salo
authors: Per
authors: P
authors: Saris
authors: Timo
authors: T
authors: Sorsa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D049452:Green Fluorescent Proteins / Q000493:pharmacokinetics; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D016177:Macrophage-1 Antigen; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
keywords: Mac-1; bioactive peptide; green fluorescent protein; leukemia; lymphoma; xenograft; αMβ2 Integrin