eiMACpro – Engineering hiPSC-derived macrophages (eiMAC) with tunable pro-inflammatory phenotype

Financiado por/Funded by:

Designação do Projeto | Project Name | eiMACpro-Engineering hiPSC-derived macrophages (eiMAC) with tunable pro-inflammatory phenotype

Código do Projeto | Project Code | 2023.11607.PEX

Domínio Científico | Scientific Domain | Ciências Médicas e da Saúde

Entidade beneficiária | Beneficiary Entity | iBET – Instituto de Biologia Experimental e Tecnológica

Data de início | Starting Date | 03.02.2025

Data de conclusão | Conclusion Date | 02.08.2026

Custo total elegível | Total Eligible Cost | 49 994,60€

Apoio financeiro público nacional | National Public Financial Support | 49 994,60€

Breve Descrição do Projeto | Brief Project Description |

Human induced pluripotent stem cells (hiPSCs) have emerged as a promising cell source for developing immunotherapies. hiPSCs offer unlimited expansion potential and are amenable to genetic manipulation, making them ideal for generating macrophages (iMACs) for standardized, off-the-shelf allogeneic therapies against solid tumors.

A major challenge in utilizing iMACs for cancer immunotherapy is their functional plasticity, which is influenced by both their developmental origin and local environmental signals. Therefore, new strategies are needed to modulate macrophage phenotypes in a controlled and context-dependent manner. Advances in genome-editing technologies—particularly inducible CRISPR systems—provide new opportunities to reprogram the behavior of hiPSC-derived immune cells with precision.

Here, we propose to generate hiPSC-derived macrophages equipped with a genetic system that allows tunable regulation of gene expression. This system will be used to target the expression of transcription factors (TFs) that govern macrophage polarization, enabling reversible and inducible control over specific macrophage functions. Our approach is designed for flexibility, allowing adaptation to different target genes and the dynamic tuning of iMAC phenotypes.

This project will deliver a versatile platform for modulating gene expression not only in hiPSC-derived macrophages but also across other hiPSC-derived cell types. The implications extend beyond macrophage-based therapies to include T cells, endothelial cells, and other immune-relevant cell types valuable for immunotherapy development and 3D cancer modeling.