Rapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology

doi:10.1021/jacs.4c11648

Rapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology

2024-10-16

0

PRE

AI

Seyed Farzad Baniahmad

DOI：10.1021/jacs.4c11648

Original

Original request for help

Save

Abstract

En 中文

Bispecific antibodies (bsAbs) are emerging immune-therapeutics, and many formats exist that differ considerably in structure. However, little systematic data exist about how the spatial organization of their components influences activity, requiring innovative approaches combining empirical and quantitative frameworks. This study presents a modular DNA nanotechnology platform to generate numerous bsAbs with surrogate geometries that span the structural features of the BiTE, IgG-like, and IgG-conjugate platforms to screen for T-cell engagement. Results highlight interesting structure-activity relationships regarding bsAb potency and selectivity and raise questions regarding the molecular phenomena underlying activity. To elucidate some effects, the platform was paired with a simple mathematical model. This work is thus one of the first to systematically investigate and reveal the importance of the spatial organization of bsAb components on activity and equally provides an accessible and convenient tool for rapidly mapping out such trends for other combinations of target epitopes.

Keywords:

SINGLE-CHAIN ANTIBODY

HUMAN IGG1

BLINATUMOMAB

STABILITY

Rapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology

Abstract

Journal

Organization