WEHI PhD Completion Seminar hosted by Associate Professor Edwin Hawkins   

Dr Jeremy Er

PhD Student – Hawkins Laboratory, Inflammation division, WEHI

4D in situ intravital data and spatial transcriptomics to define bone marrow microenvironments in myeloma

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in tapestry Lounge

Multiple myeloma (MM) is a blood cancer characterised by the expansion of malignant plasma cells in the bone marrow (BM) that leads to kidney failure, bone fractures and anaemia. Although the survival of MM patients has improved with therapeutic agents such as proteosome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies, MM remains difficult to cure. Recent T cell directing therapies (TRCT) such as CAR-T cells and bispecific antibodies have transformed the therapeutic landscape of blood cancers. Although initial response rates are high in myeloma, durable remissions have yet to be achieved with these TCRT. Thus, there is an urgent need to understand the mechanisms of resistance to design better TCRT so they can be implemented more effectively in clinical care.

Proposed mechanisms that lead to treatment failure include: (1) Loss of antigen expression (e.g. BCMA) from tumour cells due to selection pressure, (2) T cell exhaustion , (3) Alterations in tumour microenvironments, and (4) The immunosuppressive nature of specific MM clones. At present our knowledge of BM microenvironments is derived from analysis of BM aspirates that lack spatial context. Hence, the relationship and interaction of T cells within the MM microenvironments in vivo remains unknown.

Here, I will present data investigating the role of the bone marrow microenvironment in the context of immunotherapy for myeloma. By combining direct visualisation of immune cell interactions with myeloma and spatial transcriptomics, I have uncovered novel explanations for the development of resistance to bispecific antibody treatment regimes.

All welcome!