Therapeutic Monoclonal Antibodies Repurposing in Oncology via IMGT/mAb-KG Embeddings

Abstract

BackgroundCancer remains one of the leading causes of mortality world-wide, accounting for approximately 9.7 million deaths in 2022. Faced with this significant public health challenge, therapeutic monoclonal antibodies (mAbs) have emerged as promising alternatives that may minimize the side effects associated with conventional treatments such as radiotherapy and chemotherapy. To support mAb research and development, IMGT(R), the international ImMuno-GeneTics information system, has established two standardized data sources namely IMGT/mAb-DB, a comprehensive database for mAbs, and, more recently, IMGT/mAb-KG, a dedicated knowledge graph for mAbs. Despite these advances, the development of therapeutic mAbs remains both time-consuming and financially burdensome--costs can reach up to $2.8 billion. To address this challenge and accelerate cancer treatment, mAb repurposing represents a promising alternative. ResultsIn this study, we leveraged a subset of IMGT/mAb-KG, dedicated to the oncology domain, to develop a scientific hypothesis generation application for mAb repurposing. This application, based on knowledge graph embedding techniques, is designed to suggest potential mAb candidates for novel oncology applications. A user-friendly web interface provides access to the tool, incorporating visual support to facilitate the interpretation of generated hypotheses. This application is a decision support tool aiming to accelerate the discovery of new therapeutic applications for existing mAbs. ConclusionOur application demonstrates the potential of knowledge graph embedding techniques in the oncology domain by enabling the repurposing of existing mAbs for new therapeutic uses. Using this tool, we have identified two novel mAbs, loncastuximab tesirine and glofitamab, both currently undergoing clinical trials for the treatment of chronic lymphocytic leukemia. This decision-support tool thus facilitates the discovery of new therapeutic opportunities by effectively repositioning existing mAbs for oncological indications, potentially accelerating the development of cancer therapies and addressing critical public health needs.