Development of novel immune therapy for acute myeloid leukemia -Targeting immune checkpoint blockades and development of CAR-T cell therapy for acute myeloid leukemia

Acute Myeloid Leukemia (AML) treatment has remained unchanged for decades and 5-year survival rate for AML is unsatisfactory. Mutations in the tyrosine kinase receptor FLT3 are detected in 25-30% of AML patients. The most common mutation is FLT3-ITD, which is associated with inferior clinical outcome, which involves immune escape by an unknown mechanism. We recently discovered that primary FLT3-ITD positive AML cells are strongly dependent upon HSP90 for their survival. Our preliminary data also show that HSP90 promotes cell surface expression of immune checkpoint proteins, including PD-L1. This strongly suggests that HSP90 contributes to immune escape of FLT3-ITD-positive AML cells and indicating that HSP90 inhibitors are candidate drugs for immune therapy. Finally, no satisfying targets have been identified for CAR-T therapy for AML. We discovered a protein that is strictly localized to the ER in healthy cells, but which translocates from the ER to the cell surface in FLT3-ITD-positive AML cells, making it an attractive candidate for CAR-T cell therapy.  

Goal

The goal of our research is to (i) determine whether and how HSP90 underpins immune checkpoints in FLT3-ITD-positive AML cells; (ii) explore HSP90 inhibitors as immune therapy for AML; (iii) develop CAR-T cells against FLT3-ITD positive AML using a new target that is uniquely expressed on the cell surface of FLT3-ITD-positive AML cells.

 

What we offer the student

? Experience with the basic and cutting edge Cancer Molecular Medicine;

? Experience in classical biochemistry/ molecular and cellular biology methods: PCR, RT-qPCR, Western blot, gene cloning, immunofluorescence, flow cytometry;

? Experience with state-of-the-art high-throughput methods: RNA-seq, mass spectrometry;

? Training in transferrable skills: presentations, writing, project planning;

? One member of an international research team with researchers at different stages of their careers;

? Frequent opportunities to discuss your data (weekly lab meetings) and to get updated on the most recent advances in the relevant field (“journal club” presentations);

? An ambitious and friendly environment where team members share their expertise to get better;

Our research group

The “Cancer Molecular medicine” research group headed by Prof. Jorrit Enserink consisted of twelve members from six different countries. One of our research areas is personalized medicine for AML with the development of novel therapies. The group is a young and dynamic environment and has long experience in supervision of master and PhD students. Our group is part of the Department for Molecular Cell Biology in Institute for Cancer research at Radiumhospitalet, where we share facilities, reagents and expertise with other groups in a good and professionally challenging working environment.

 

Published Mar. 22, 2018 10:29 AM - Last modified Apr. 19, 2018 8:13 AM

Supervisor(s)

Scope (credits)

60