Baculovirus-insect cell production of bioactive choriogonadotropin- immunoglobulin G heavy-chain fusion proteins in sheep

Abstract

A hybrid cDNA encoding a fusion protein between the beta subunit of hCG (βhCG) 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 βhCG-CH1-3 in the presence of complement. Intravenous injection of βhCG-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.