![Capturing the complexity of the leukemic bone marrow microenvironment [acronym: BM-LIME]](https://cdn.prod.website-files.com/6a72d3824b93a65025d38466/6aa3f2d746b7fcda87a4baaf_6aa3e3f8b80a99865a9ec49d_bone-marrow-leukemia-and-immuno-microenvironment-3d3a19.avif)
Capturing the complexity of the leukemic bone marrow microenvironment [acronym: BM-LIME]
To build a bone marrow-on-a-chip microfluidics model to study the leukemia-induced changes in the immuno-microenvironment
This project is aimed to develop a 3D-model that captures the complexity of the human bone marrow (BM) including supportive tissues and immune cells. A representative model is essential to elucidate leukemia-induced changes in the bone marrow microenvironment that suppress immune cell function and in that way jeopardizes the efficacy of immunotherapy. In this public-private partnership, we combine expertise in the pathobiology of pediatric acute leukemia (Den Boer group – Princess Máxima Center for Pediatric Oncology) and organ-on-a-chip technology (MIMETAS BV) to build such a human bone marrow-reflecting 3D model.
Unmet need: Cell-based immunotherapies are currently only ‘effective’ if the leukemic burden in the bone marrow (BM) is below 5%.
Why: the BM-microenvironment created by leukemic cells is immunosuppressive. Immune cell migration to leukemic cells is obstructed and/or effector function of immune cells is inhibited.
What is needed: Representative BM-models that capture the complexity of the BM at disease and allows to study immune cell recruitment to BM and ways to sensitize to immunotherapy.
Approach and deliverables: We will generate a 3D BM-model including the supportive cell types and immune cells in a ratio observed in leukemic patients, and build a mini-vein mimicking a blood vessel to study migration dynamics of immune cells to the leukemia-containing compartment. This model will be used to functionally elucidate causes of immunosuppression and allows the testing of new (immunomodulatory-)agents, bispecific antibodies, and CAR-products that may enhance patients’ response to cell-based immunotherapies.
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