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Effectiveness of anti-folate receptor beta antibody conjugated with truncated Pseudomonas exotoxin in the targeting of rheumatoid arthritis synovial macrophages.

Research paper by Ryusaku R Nagayoshi, Taku T Nagai, Kakushi K Matsushita, Katsuaki K Sato, Nobuhiko N Sunahara, Takemasa T Matsuda, Tadashi T Nakamura, Setsuro S Komiya, Masanori M Onda, Takami T Matsuyama

Indexed on: 06 Sep '05Published on: 06 Sep '05Published in: Arthritis and rheumatism



Abstract

To define the distribution of folate receptor beta (FRbeta)-expressing cells in various tissues, including rheumatoid arthritis (RA) synovial tissues, and to verify the effects of an immunotoxin composed of an anti-FRbeta monoclonal antibody (mAb) and truncated Pseudomonas exotoxin A (PEA) on apoptosis and tumor necrosis factor alpha (TNFalpha) production by adherent synovial mononuclear cells from RA patients.Anti-FRbeta mAb were produced by immunizing mice with FRbeta-transfected murine pre-B cells. The distribution of the FRbeta antigen was examined by immunohistochemical analysis using anti-FRbeta mAb and macrophage-specific anti-CD163 mAb. Anti-FRbeta mAb was chemically crosslinked with truncated PEA. FRbeta-expressing macrophages were produced by the transfection of adenovirus vector containing the FRbeta gene. Apoptotic cells were detected by staining with propidium iodide. TNFalpha was measured by enzyme-linked immunosorbent assay.FRbeta-expressing cells were not present in peripheral blood leukocytes and their activated cells. In all of the tissues examined, most FRbeta-expressing cells were CD163+. The immunotoxin significantly induced the apoptosis of FRbeta-transfected macrophages and adherent RA synovial mononuclear cells and inhibited TNFalpha production by adherent RA synovial mononuclear cells.We demonstrated the limited distribution of FRbeta-expressing cells in various tissues. The immunotoxin targeting FRbeta-expressing cells will provide a therapeutic tool for rheumatoid synovitis.

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