Construction of an immunotoxin by linking a monoclonal antibody against the human epidermal growth factor receptor and a hemolytic toxin.
Hybrid molecules obtained through conjugation of monoclonal antibodies and toxins constitute an approach under exploration to generate potential agents for the treatment of cancer and other diseases. A frequently employed toxic component in the construction of such immunotoxins is ricin, a plant toxin which inhibits protein synthesis at ribosomal level and so requires to be internalized by the cell. A hemolytic toxin isolated from the sea anemone Stichodactyla helianthus, which is active at the cell membrane level, was linked through a disulfide bond to the anti-epidermal growth factor receptor monoclonal antibody ior egf/r3. The resulting immunotoxin did not exhibit hemolytic activity except under reducing conditions. It was toxic for H125 cells that express the human epidermal growth factor receptor, but non-toxic for U1906 cells that do not express this receptor.
Unidad de Evaluación e Investigación de Productos Antitumorales, Instituto Nacional de Oncología y Radiobiología. adavila@infomed.sld.cu
Ana D
AD
Avila
Carlos F
CF
Calderón
Rita M
RM
Pérez
Carmen
C
Pons
Celia M
CM
Pereda
Ana R
AR
Ortiz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D012615:Sea Anemones / Q000737:chemistry*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D066246:ErbB Receptors