Chimeric CLL-1 Antibody Fusion Proteins Containing Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-2 With Specificity for B-Cell Malignancies Exhibit Enhanced Effector Functions While Retaining Tumor Targeting Properties

摘要: Although monoclonal antibody (MoAb) therapy of the human malignant lymphomas has shown success in clinical trials, its full potential for treatment hematologic malignancies yet to be realized. To expand a promising human-mouse chimeric antihuman B-cell MoAb (chCLL-1) constructed using variable domains cloned from murine Lym-2 (muLym-2) hybridoma, fusion proteins containing granulocyte-macrophage colony-stimulating factor (GM-CSF) (chCLL-1/GM-CSF) or interleukin (IL)-2 (chCLL-1/IL-2) were generated and evaluated vitro cytotoxicity vivo tumor targeting. The glutamine synthetase gene amplification system was employed high level expression recombinant proteins. Antigenic specificity confirmed by competition radioimmunoassay against ARH-77 myeloma cells. activity chCLL-1/GM-CSF established colony formation assay, bioactivity chCLL-1/IL-2 supporting growth an IL-2-dependent T-cell line. Antibody-dependent cellular target cells demonstrated that both mediate enhanced cell lysis mononuclear Finally, biodistribution imaging studies nude mice bearing xenografts indicated specifically tumors. These data suggest have as immunotherapeutic reagents malignancies.