Developing new antibody-based therapeutics for neuroblastoma

Metastatic neuroblastoma is a cancer of the nervous system that kills the majority of the affected children. Although there have been tremendous advances in the understanding of the molecular causes of the disease, patients are still treated with highly toxic mixtures of chemicals and radiation. Thus, safer, innovative approaches for this cancer are urgently needed. We propose to evaluate the efficacy of antibodies for neuroblastoma therapeutics. Antibodies are proteins that can bind to cells, triggering their death by engaging the immune system. Antibodies can also be engineered to carry cancer-killing molecules that are delivered specifically to tumour cells, while sparing normal tissues.
The aim of the project is to pre-clinically validate a newly developed monoclonal antibody for neuroblastoma therapeutics. The anti-LGR5 antibody (called BNC101) has been originally developed to target colon cancer stem cells. We will use the reagent in experiments whose primary objective is to evaluate the ability of the antibody to induce cancer regression in vitro and in vivo, especially in the context of patient-derived xenografts (PDX). A secondary aim is to clarify mechanisms of action, safety and identify biomarkers that predict clinical response. The project is ideally suited to a student with an MD or first or upper second undergraduate degree in cell biology, molecular biology or pharmacology. Familiarity with cancer cell cultures and basic biochemical and molecular techniques is also essential.