Accelerating antibody discovery and optimization with high-throughput experimentation and machine learning.

Abstract

The integration of high-throughput experimentation and machine learning is transforming data-driven antibody engineering, revolutionizing the discovery and optimization of antibody therapeutics. These approaches employ extensive datasets comprising antibody sequences, structures, and functional properties to train predictive models that enable rational design. This review highlights the significant advancements in data acquisition and feature extraction, emphasizing the necessity of capturing both sequence and structural information. We illustrate how machine learning models, including protein language models, are used not only to enhance affinity but also to optimize other crucial therapeutic properties, such as specificity, stability, viscosity, and manufacturability. Furthermore, we provide practical examples and case studies to demonstrate how the synergy between experimental and computational approaches accelerates antibody engineering. Finally, this review discusses the remaining challenges in fully realizing the potential of artificial intelligence (AI)-powered antibody discovery pipelines to expedite therapeutic development.