Novel antibody-based drugs to treat breast cancers with limited treatment options

Project description

Human Epidermal Growth Factor Receptor 2 Positive (HER2+) and Triple Negative Breast Cancer (TNBC) are more prevalent in younger women than in older women and both have limited treatment options and poor overall survival outcomes. Antibody-drug conjugates have become a promising approach for delivering drugs or toxins directly to tumours by using antibodies that specifically bind tumour cells or the surrounding tumour environment, that support tumour growth. However, they face challenges—current antibody-drug conjugates have a narrow window between effectiveness and harmful side effects, and tumours often develop resistance to treatment by actively removing the toxins.

Professor Andrew Scott and colleagues have developed novel antibodies that bind a tumour specific form of HER2, and EphA3 which is a protein found in the tumour microenvironment of diverse breast tumour types, particularly TNBCs. In this NBCF-funded study the team will attach these antibodies to a novel toxin, aiming to deliver the drug directly to the tumours and stop their growth.

This toxin is proving to be an effective payload, with early clinical trials now underway. These novel antibody-drug conjugates will be tested in laboratory models of breast cancer to assess their uptake in tumours and their effects on tumour growth. The team will also assess how the antibody-drug conjugates affect tumour immunity and whether they can improve the effectiveness of immunotherapies, which have been less successful in treating breast cancer.

Why is this work needed

HER2+ and TNBC are aggressive forms of breast cancer that are more likely to spread, making them difficult to treat. Therefore, there is a need to develop new therapies that are more effective against these tumours while minimizing harmful side effects.

Expected outcomes

The successful outcomes of this study will define the effectiveness, safety and tumour specificity of novel antibody-drug conjugates in diverse HER2+ and TNBC tumour laboratory models.