ABSTRACT
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.
Subject(s)
Animals , Humans , Mice , Antibodies, Monoclonal/chemistry , Hemolysis/drug effects , Immunotoxins/chemistry , ErbB Receptors/metabolism , Sea Anemones/chemistry , Tumor Cells, Cultured/drug effects , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/metabolism , Electrophoresis, Polyacrylamide Gel , Immunohistochemistry , Immunotoxins/pharmacology , ErbB Receptors/drug effects , Tumor Cells, Cultured/cytologyABSTRACT
We evaluated the effect of the conjugate of basic fibroblast growth factor (FGF2) and saporin (FGF2-SAP) on proliferation of cultured keratocytes. Cultured rabbit and human keratocytes were incubated in medium containing 0.01 to 100 nM of chemical conjugate of EGF2 conjugated by disulfide bond to saporin (CCFS1), FGF2 genetically fused to saporin (rFGF2-SAP), FGF2, or saporin for three hours or four days and cell proliferation was quantified four days after the drug treatment. Proliferation of rabbit and human keratocytes was effectively inhibited by three hour and by four day exposure to CCFS1 and rFGF2-SAP in a dose-dependent manner, whereas it was affected minimally by four day exposure to saporin. Their inhibitory effects were detected at concentrations above 0.1 or 1 nM, and were most prominent in serum-stimulated rabbit keratocytes. These results suggest a potential role for FGF2-SAP in limiting proliferation of keratocytes during corneal wound healing.
Subject(s)
Animals , Humans , Rabbits , Antineoplastic Agents, Phytogenic/pharmacology , Cell Division/drug effects , Cell Line , Cells, Cultured , Corneal Stroma/cytology , Dose-Response Relationship, Drug , Fibroblast Growth Factor 2/pharmacology , Immunotoxins/pharmacology , N-Glycosyl Hydrolases , Plant Proteins/pharmacology , Ribosome Inactivating Proteins, Type 1ABSTRACT
Los efectos adversos de la quimioterapia antitumoral y de la radioterapia, ocasionan en el paciente una serie de manifestaciones que resquebrajan su calidad de vida y a las cuales se deben sumar, además, los estragos ocasionados por su enfermedad de fondo. En muchos casos la quimioterapia y la radioterapia, cuando una cirugía radical no ha sido definitiva, sólo complementan el tratamiento y no van más allá de un temporal estado remisivo, antes de la etapa final. La necesidad de atacar a la célula tumoral en forma selectiva, buscando en ellos antígenos específicos, ha hecho que en los últimos años se venga desarrollando una moderna alternativa antitumoral: las inmutoxinas y las toxinas recombinantes