Project description
Miniature bone organs for modelling immunotherapy response
Therapy using chimeric antigen receptor T (CAR-T) cells has demonstrated great clinical efficacy for certain haematological malignancies. However, it remains largely ineffective against acute myeloid leukaemia, possibly due to the bone marrow microenvironment, which can suppress immune responses and protect leukaemia cells from attack. Understanding how this microenvironment undermines CAR-T therapy requires better experimental models. The ERC-funded ImmunhOss project builds on a novel technology that faithfully recapitulates the patient bone marrow microenvironment. These humanised miniature bone organs will be used to map immune regulatory interactions, model CAR-T therapy responses, and test strategies to overcome leukaemia resistance. Project findings will help advance personalised immunotherapy for this devastating disease.
Objective
ImmunhOss proposes the personalized modelling of cellular immunotherapies towards improving their efficacy in leukemia context.
Cellular immunotherapies hold great clinical promises after demonstrating spectacular success in lymphomas and multiple myeloma, through the pioneering Chimeric Antigen Receptor T cells (CAR-Tc) strategy. However, the outcome remains poor for acute myeloid leukemia (AML) which accounts for the majority and most lethal adult leukemia. Pre-clinical successes were not followed by clinical efficacy, pointing at the substantial discrepancy between mouse models and patient response. In AML, evidence suggest a key role of the human bone marrow microenvironment, capable of acting both as a pro-inflammatory and immuno-suppressive unit.
Towards decoding the bone marrow functions in AML, my laboratory has successfully developed humanized ossicles (hOss), as miniaturized bone organs forming ectopically in mice. Those were shown to reconstitute the patient bone marrow microenvironment, leading to the superior AML engraftment and the individualized recapitulation of chemotherapy responses.
ImmunhOss builds on the unique hOss technology to uncover the immuno-regulatory roles of the human bone marrow upon CAR-Tc therapy. By detailed and interaction mapping between immune, bone marrow and AML cells (WP 1), I will validate the existence and composition of immuno-regulatory niches. Temporal modelling of CAR-Tc therapy in hOss will reveal potential changes in these niches and uncover mechanisms of AML resistance (WP 2). Finally, I propose using hOss to test strategies for enhancing CAR-Tc effectiveness by targeting identified bone marrow immune niches (WP 3).
By integrating cancer immunology and personalized tissue engineering, ImmunhOss is particularly timely as addressing the critical need for highly relevant tools capable of modelling immunotherapy response.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2025-COG
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22100 Lund
Sweden
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