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Decoding the immuno-regulatory functions of the human bone marrow niche upon cancer cellular therapy

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.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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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Host institution

LUNDS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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