T Cell Receptor Based Immunotherapeutics Targeting FLT3-TKD Mutated Acute Myeloid Leukaemia
Preclinical validation T cell engagers and cell therapies for treatment of of FLT3-TKD specific Acute Myeloid Leukaemia
In this project the LUMC and Imuno BV will develop two different types of immunotherapies to treat patients with Acute Myeloid Leukaemia (AML), in particular AML caused by mutations in an important domain of the FLT3 protein, the so-called tyrosine kinase domain (FLT3-TKD).
AML is an aggressive type of blood cancer that originates from malignant myeloid progenitor cells in the bone marrow. AML is caused by DNA mutations, and 7-10% of the patients have FLT3-TKD mutations. Most patients initially respond to standard therapies, but the disease comes back in approximately half of the patients. Patients who fail to respond and patients with disease recurrence after standard therapies have an extremely poor prognosis often ranging between 3 to 9 months if there are no treatment options anymore.
Imuno BV will develop antibodies that can bind to T cells as well as AML cells with FLT3-TKD mutations. LUMC will develop immunotherapy in which T cells are genetically engineered with a receptor that can bind to AML cells with FLT3-TKD mutations. In both types of immunotherapies, T cells are stimulated to kill the tumor cells. Experiments will be performed to investigate and compare the safety and capacity of the two immunotherapies to kill tumor cells. These experiments will be performed in a culture dish as well as in mouse models.
The project will deliver a new immunotherapy that can be further developed and tested in a clinical study for its safety and potential to cure and increase the life expectancy of patients with FLT3-TKD mutated AML.
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