Multiple myeloma is a blood cancer that develops in the bone marrow from malignant plasma cells. Using a mouse model of multiple myeloma, we have recently demonstrated the importance of the immune system, and T cells in particular, in controlling myeloma growth in vivo. We have also established that anti-CD137 mAb immunotherapy induces potent T cell responses and protects mice against multiple myeloma. T cells are known to recognize tumour-specific neoantigens (i.e. altered proteins that arise from nonsynonymous somatic mutations occurring in cancer cells). However, there is no available model allowing the study of myeloma-specific responses in vivo. This project aims to develop tools to investigate antigen-specific responses in a mouse myeloma model. We will analyse naturally arising antigen-specific responses and responses generated following immunotherapy.
- To identify naturally occurring antigen-specific immune responses to multiple myeloma.
- To investigate the evolution of neoantigen landscape during immunotherapy treatment of multiple myeloma.
- To determine the effect of immunotherapy on the quality and quantity of tumour antigen-specific cells in relation with anti-tumour efficacy.
The following techniques will be used: in vitro culture, animal experimentation, flow cytometry, electrophoresis, ELISPOT.
The development of antigen-specific T cell responses represents a key step in the establishment of a protective and long-lasting immune response against cancer. This project will develop the first model allowing the study of antigen-specific immune responses against multiple myeloma. This model will be extremely useful to the development of new effective immunotherapies against this blood cancer.
- This project is suitable for a PhD student but some components of this project may be undertaken by an Honours or Masters student. Some background in Immunology is highly desired.