Optimising antibody-drug conjugate therapies for high-risk B-cell acute lymphoblastic leukaemia

This project is suitable for Honours, Masters (by Research) and PhD students. Background B-cell acute lymphoblastic leukaemia (B-ALL) remains a major therapeutic challenge for patients with relapsed or treatment-resistant disease. Although antibody-drug conjugates (ADCs) have transformed the treatment of several cancers by enabling selective delivery of highly potent cytotoxic agents, understanding the biological factors that determine efficacy, resistance and toxicity remains a major challenge. Our laboratory is developing innovative preclinical models to optimise the next generation of ADC-based therapies for B-ALL. This includes the development of a novel humanised CD74 mouse model, enabling clinically relevant evaluation of CD74-targeted therapeutics in vivo. By combining patient-derived xenograft (PDX) models with advanced molecular profiling, this project aims to better understand how ADCs eliminate leukaemia cells, identify biomarkers predicting therapeutic response, and develop strategies to improve efficacy while minimising toxicity. Aim This project will investigate the preclinical activity of next-generation antibody-drug conjugates in high-risk B-ALL using innovative humanised mouse models and clinically relevant patient-derived xenografts. Students will receive training in cutting-edge translational research techniques, including: development and characterisation of humanised mouse models patient-derived xenograft (PDX) models antibody-drug conjugate pharmacology and targeted therapy evaluation molecular mechanisms of therapeutic response and resistance single-cell transcriptomics, proteomics and genomic profiling biomarker discovery and translational data integration. This project provides an exciting opportunity to contribute to the development of next-generation targeted therapies for patients with high-risk B-cell acute lymphoblastic leukaemia. Essential criteria Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum