Baculovirus-insect cell production of bioactive choriogonadotropin-immunoglobulin G heavy-chain fusion proteins in sheep.
A hybrid cDNA encoding a fusion protein between the beta subunit of hCG (beta hCG) and constant domains of a mouse IgG heavy chain (CH1-3) was inserted into a baculovirus expression vector. Insect cells transfected with foreign DNA synthesized multimeric forms of fusion protein that inhibited hCG-induced steroid hormone secretion by mouse Leydig tumor cells. Leydig cells were lysed by beta hCG-CH1-3 in the presence of complement. Intravenous injection of beta hCG-CH1-3 in rams was associated with testicular mononuclear leukocyte infiltration, interstitial tissue damage, and a transient depression in circulatory testosterone (levels returned to normal within 2 wk). It appears that targeted cell-killing can be mediated by recombinant proteins composed of the receptor-binding moiety of hormones and truncated effector (Fc) regions of lethal antibodies.
Johnson
G A
GA
Department of Animal Science, University of Wyoming, Laramie 82071.
Hansen
T R
TR
Austin
K J
KJ
Van Kirk
E A
EA
Murdoch
W J
WJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D017924:Nucleopolyhedroviruses / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012756:Sheep; D018411:Spodoptera; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006063:Chorionic Gonadotropin; D017931:DNA Primers; D018076:DNA, Complementary; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011993:Recombinant Fusion Proteins; D013739:Testosterone