Targeting immuno-oncology molecules in blood cancers

Can be adapted in scope for Honours or Masters

BACKGROUND

Although immunotherapy has emerged as an important treatment option, it is still challenging to achieve durable clinical responses by immunotherapy. Using preclinical models and clinical samples, the project aims to understand 1) how cancer cells escape the immune system and 2) how we can improve efficacies of immunotherapeutic drugs.

APPROACH

• Targeting stress-adaptive pathways to improve immune-mediated control of blood cancers.
• Understanding effector mechanisms of bispecific T-cell engaging antibodies.
• Harnessing innate immunity to improve efficacies of antibody drugs.

METHOD

The student will learn the following research techniques: 1) in vivo leukaemia models (animal handling, various drug treatments, bioluminescence imaging), 2) in vitro cell culture (gene transduction, T cell stimulation assays, macrophage activation assays) 3) flow cytometry analysis, and 4) immunoblot analysis.

REFERENCES

1. Salik et al. Targeting immune checkpoints in hematological malignancies. Journal of Hematology & Oncology 2020. 13 (1), 1-19
2. Nakamura et al. Cancer immunoediting and immune dysregulation in multiple myeloma. Blood 2020. 36 (24), 2731-2740
3. Nakamura et al. Targeting an adenosine-mediated “don’t eat me signal” augments anti-lymphoma immunity by anti-CD20 monoclonal antibody. Leukemia 2020. 34 (10), 2708-2721
4. Nakamura et al. Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell 2018. 33 (4), 634-648.