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Blinatumomab in relapsed acute lymphoblastic leukaemia

This honours project will investigate resistance mechanisms to the bispecific T-cell engager (BiTE) blinatumomab in relapsed acute lymphoblastic leukaemia.

Recently, a new compound of drug known as Bispecific T-cell engager (BiTE) has been approved for use in B-ALL by the Food and Drug Administration (FDA) and is currently undergoing clinical trials in Australia. Blinatumomab is a BiTE that enables an immunological response between the CD19 positive leukaemic cell and a cytotoxic CD3 positive T-cell.

While the introduction of blinatumomab promises to be an exciting addition to the clinical arsenal, initial response rates in relapsed/refractory ALL have been ~43% and, as with other treatments, resistance is likely to occur. Immune evasion is a likely cause of resistance as well as loss of the CD19 target, leading to CD19 negative relapse and further investigation is warranted.

Relapsed patient samples that are identified as being treated with blinatumomab will be flow sorted by CD19 positivity. CD19 positive and CD19 negative populations will undergo mRNAseq to identify if a lineage switch has occurred and if the driving event is now present in the CD19 negative population. Differences in gene expression will also be interrogated.

Resistance will be modelled in-vitro by subjecting fusion constructs to incrementally increasing doses of blinatumomab, enabling further examination of potential immune evasion pathways.

Professor Deborah White

Supervisors

Professor Deborah White

Co-supervisors: Dr Sue Heatley

Research area: Cancer program - South Australian Health and Medical Research Institute

Recommended honours enrolment: Honours in Molecular and Biomedical Science

Tagged in Honours projects - Molecular and biomedical science, Honours projects - Deborah White, Honours projects - Molecular and biomedical science: Biochemistry, Honours projects - Molecular and biomedical science: Microbiology and immunology, Honours projects - Susan Heatley