Assess efficacy of human-specific CCR8 therapeutics with higher translatability

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In our latest scientific article published in Frontiers in Immunology, we characterize the genO-BRGSF-HIS mouse model — a mouse model implanted with human CD34⁺ hematopoietic stem cells and boosted with human Flt3L, which leads to the development of human functional lymphoid, myeloid and dendritic cell compartments.

You can read the full article here or 🎬 watch the webinar presented by one of the authors.

Below are some key data published in this paper.

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The genO-BRGSF-HIS mouse develops a functional myeloid compartment

Characterization of the myeloid cells in the genO-BRGSF-HIS model shows that they express different toll-like receptors and that these cells are functional. This was demonstrated by stimulating human myeloid cells with different TLR agonists, which leads to increased expression of activation markers such as CD83 on monocytes.

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Human myeloid cells respond to different stimuli

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The immune cell composition of tumors is dependent on tumor burden in genO-BRGSF-HIS mice

For the characterization of the tumor microenvironment (TME) in this model, genO-BRGSF-HIS mice were implanted with different tumor cell lines.

As shown in the figure below, the TME of A549 tumors in genO-BRGSF-HIS mice show a dynamic immune cell composition depending on the tumor size analysed. The recruitment of immune cells to the TME shows that the human immune cells are capable of detecting different stimuli, further highlighting that these cells are functional.

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Dynamic A549 TME composition over time​

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The immune cell composition of tumors also changes according to tumor type

We show that the TME composition of MDA-MB-231 tumors in the genO-BRGSF-HIS model is very different from that of A549 tumors, demonstrating that the immune cell composition is dependent on tumor type.

As shown below, in MDA-MB-231 tumors there is a prevalence of human M2-like macrophages, while in the A549 tumors had a high percentage of human NK cells. The presence of M2-like macrophages also shows that the human immune cells are polarized, and hence, functional.

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TME composition in MDA-MB-231 tumors

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A stable humanization in genO-BRGSF-HIS mice enables a long therapeutic window without side effects

Humanization rate in the genO-BRGSF-HIS model is stable and lasts at least 31 weeks without associated side-effects, which enables long therapeutic windows.

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Stable humanization rates over 31 weeks

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