Human immune cell composition of TME depends on tumor cell line-derived xenograft subtype and tumor burden in genO-BRGSF-HIS mice

Background

The relevance of preclinical models has vastly improved with mice bearing a human immune system, especially in the context of immunotherapy. genO-BRGSF (BALB/c Rag2^-/-, IL2Rγ^-/-, SIRPα^NOD and Flt3^-/-) is a highly immunodeficient mouse featuring reduced murine myeloid cells. genO-BRGSF mice reconstituted with human cord blood CD34+ cells (genO-BRGSF-HIS) develop functional lymphoid and myeloid compartments. This engraftment is stable for over a year⁽¹⁾ and mice do not develop GvHD. Additionally, t h e myeloid compartment can be transiently boosted with exogenous human Flt3L injections. In contrast to other models that overexpress human cytokines to develop human myeloid cells, Flt3L-treated genO-BRGSF-HIS mice do not show side effects. genO-BRGSF-HIS mice are permissive to mouse and human cancer cell line engraftment, hence representing a valuable preclinical model to study cancer development and evaluate novel therapeutics.

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