Project: Targeting of exhausted T cells to improve immunity to chronic infections and cancer
Utzschneider Group
T cells are an important arm of the body’s immune response that can mediate protection from various infections. However, chronic viral infections as well as neoplasia are facilitated by functionally impaired 'exhausted' T cell responses. Exhausted T cells have a reduced ability to kill virus-infected or tumour cells, which is partly mediated through expression of immune ‘checkpoints’ such as PD-1. Blocking PD-1 activity augments T cell-mediated immunity and has revolutionized our approach of treating cancer patients. Despite its unparalleled success, however, checkpoint blockade does not revert the functional impairments linked to T cell exhaustion, which constitutes a critical limitation in utilizing the full potential of the body’s immune response. Work by our lab and others has identified a subset of exhausted T cells that retain proliferative and developmental potential and, more importantly, are responsible for the proliferative burst following checkpoint blockade. These so-called ‘precursors of exhausted’ T cells serve as the primary targets of therapies that aim to functionally re-invigorate exhausted T cells. This project utilizes state-of-the-art gene editing technology to target these precursors of exhausted T cells with the overarching goal to overcome exhaustion and improve immune response to chronic infections and in cancer.
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Utzschneider Group
2 vacancies
CD8+ T cells persistently exposed to antigen, such as during chronic viral infections and in tumors, undergo substantial functional and phenotypic changes, a state widely known as T cell ‘exhaustion’. This includes impairments in effector function and elevated expression of inhibitory receptors such as PD-1. Inhibitory receptors constitute critical checkpoints in T cell activation and their expression represents a major mechanism by which T cell proliferation and function are limited. Blocking the activity of PD-1 augments T cell mediated immunity and has revolutionized our approach to the treatment of many cancers. However, despite the unparalleled success of this so-called checkpoint blockade, it does not revert the functional impairments linked to T cell exhaustion, which constitutes a critical limitation in utilizing the full potential of the body’s immune response.
Our group studies the mechanisms inducing T cell exhaustion with the ultimate goal to identify targets that can lead to the design and development of novel therapeutic treatments to improve health of patients suffering from chronic infections or cancer.
Utzschneider Group Current Projects
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Integrating multiomics to decipher regulators of T cell function in chronic infection and cancer
PhD/MPhil, Master of Biomedical Science
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Targeting of exhausted T cells to improve immunity to chronic infections and cancer
PhD/MPhil, Master of Biomedical Science, Honours
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Next generation humanised mouse platform to fast-track therapeutic discovery
PhD/MPhil, Master of Biomedical Science, Honours
Research degrees at the Doherty Institute are administered by the University of Melbourne.