genO-BRGSF-HISマウスにおいて、腫瘍細胞株由来の異種移植片のサブタイプが腫瘍微小環境の構成を決定づける

背景

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 over a year(1) and mice do not develop GvHD. Additionally, the myeloid compartment can be transiently boosted with exogenous human Flt3L injections. In contrast to other models which 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 and represent a valuable preclinical model to study cancer development and evaluate novel therapeutics.

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