Background: Bispecific heterodimeric antibody consisting of two different heavy chains and two different light chains requires heterodimerization of heavy chains and cognate light-heavy chain pairings. Results: Cognate light-heavy chain pairing can be achieved by an antibody engineering approach. Conclusion: Bispecific hetero-IgG antibodies can be made in mammalian cells. Significance: The technology could be used in the production of bispecific antibodies for many biotechnological applications.
Background: Co-crystal structure of Fc-Fc␥RIII complex revealed that Fc binds to Fc␥RIII asymmetrically. Results: We identified a panel of novel Fc heterodimers with enhanced ADCC activity. Conclusion: Asymmetrical Fc engineering is an efficient approach for enhancing ADCC activity and stability of engineered antibodies. Significance: The discovery could be applied in therapeutic antibodies for the treatment of cancers and infectious diseases.
We have examined the human Cyr61 gene and its expression in normal fibroblasts. The core promoter, second intron, and 3' untranslated region (UTR) are highly conserved between the human and mouse genes. Cyr61 expression was induced slightly slower but more transiently in human fibroblasts compared to Rat-2 fibroblasts. These differences may relate to the absence of a serum response element in the human Cyr61 promoter, and the presence of additional AU-rich elements within the 3' UTR. Cycloheximide causes accumulation of human Cyr61 RNA in the absence of growth factors, and EGF prevents decay of transcripts in actinomycin-D-treated cells, which suggests that induction by growth factors may partially involve mRNA stabilization. We detect an alternative RNA in serum-stimulated fibroblasts containing an in-frame deletion within exon 4 which disrupts the thrombospondin type 1 repeat. Constitutive expression of the full hCyr61 genomic DNA in rodent fibroblasts causes production of multiple protein species, whereas expression of hCyrDelta4 produces a single stable protein of the expected size. We also observed multiple hCyr61 protein species in normal fibroblasts following serum stimulation, indicating that Cyr61 may normally be produced as alternative isoforms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.