Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

I-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists

ABSTRACT: i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists

PROVIDER: PRJNA1033696 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists

Project description:The ability to leverage antibodies to agonize disease relevant biological pathways has the potential to unlock new drug targets for clinical investigation. While antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biological activity of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Herein, we describe a novel engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. Thus, iAb engineering represents a new tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

2023-12-18 | GSE246602 | GEO

i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.

Project description:The ability to leverage antibodies to agonize disease relevant biological pathways has tremendous potential for clinical investigation. Yet while antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biology of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Here, we describe an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. iAb engineering provides a tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

| S-EPMC10799922 | biostudies-literature

Shaped Chain Elongating Microbiome

Project description:Shaped Chain Elongating Anaerobic Microbiome Raw sequence reads

| PRJNA686230 | ENA

Opioid agonists as potential AML therapy

Project description:Opioid agonists as potential AML therapy

| PRJNA615085 | ENA

Inverse Agonists of the Androgen Receptor

Project description:Inverse Agonists of the Androgen Receptor

| PRJNA848752 | ENA

Methanosarcina spindle-shaped virus 1

Project description:Methanosarcina spindle-shaped virus 1 Metagenomic assembly

| PRJNA1132277 | ENA

Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages

Project description:This SuperSeries is composed of the following subset Series: GSE25137: Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human expression GSE25426: Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human ChIP-Seq Refer to individual Series

2011-12-01 | E-GEOD-25608 | biostudies-arrayexpress

TLR agonists on human dendritic cells

Project description:Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists.. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h Keywords: other

2005-09-01 | GSE2706 | GEO

Nitrosopumilus spindle-shaped virus

Project description:Nitrosopumilus spindle-shaped viruses (NSV) of genome sequencing and assembly

| PRJNA516109 | ENA

Unexpected conformational variations of the human centromeric chromatin complex

Project description:Unexpected conformational variations of the human centromeric chromatin complex

| PRJNA413913 | ENA