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Lymphocyte specific kinase inhibitors for controlling immunotherapy toxicity

36 months
Approved budget:
Associate Professor Jack Flanagan
Dr Julie Spicer
Dr Kimiora Henare
Professor Joseph Trapani
Dr Jiney Jose
Dr Jagdish Jaiswal
Professor Peter Shepherd
Professor William Denny
Dr Swarna Gamage
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
Turning on a type of white blood cell called T-cells to seek out and kill cancer cells is a major advance in cancer therapy. These "living drugs" have durable responses in some patients, but their toxicity ranges from mild immune responses to life-threatening tissue destruction. Toxicity management does not directly control T-cell function, but relies on non-specific, anti-inflammatory effects that can kill T-cells or block the action of proteins called cytokines. T-cells can be controlled without destroying them by blocking an enzyme called lymphocyte specific kinase (Lck). We have discovered a new class of highly potent and selective Lck inhibitors. The aim of this project is to optimise this class of compounds and select a candidate molecule for extensive pre-clinical development.