Designer cytokines: targeting actions to cells of choice.
Some growth factors are therapeutically useful partly because restricted expression of their receptors limits their action to particular cell types. However, no unique stimulatory factor is known for many clinically relevant cell types, such as CD34+ hematopoietic stem cells. Here, soluble alpha receptor (R alpha) components for interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) were targeted in an active form to cells expressing surface markers such as CD34 or CD45, thereby rendering those cells responsive to IL-6 or CNTF. The targeting of R alpha components may provide the means to create "designer" cytokines that activate a desired cell type expressing a specific cell surface marker.
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018952:Antigens, CD34 / Q000032:analysis; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D017493:Leukocyte Common Antigens / Q000032:analysis; D008222:Lymphokines; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010766:Phosphorylation; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine / Q000378:metabolism; D011961:Receptors, Fc; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D017475:Receptors, Nerve Growth Factor / Q000276:immunology / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012995:Solubility; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D007141:Immunoglobulin Fc Fragments; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D011961:Receptors, Fc; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D017475:Receptors, Nerve Growth Factor; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130; D017493:Leukocyte Common Antigens