327 Humanized mouse models for characterizing growth and tissue infiltration of luciferase-expressing AML cell lines

Background

Leukemia, notably Acute Myeloid Leukemia (AML), a prominent subtype, is a major health concern worldwide, marked by high mortality rates. Despite the recent improvements of conventional treatments such as chemotherapy, there remain significant gaps in their efficacy, tolerability and resistance, necessitating innovative therapeutic strategies. This study addresses this need by developing murine models of AML more closely emulating the clinical setting for improved therapeutic evaluations. The recent advancement of the Humanized Immune System (HIS) mice model has opened new horizons for cancer immunology and immunotherapy research. By facilitating the engraftment of human tumor and immune cells, HIS models provide a platform for studying tumor-associated immunology, immunotherapy drugs, and tumor-immune cell interactions. Its application extends to assessing immune-checkpoint inhibitors and cell therapies, in particular CAR-T cells.

Methods

Our study established three AML models in humanized mice, incorporating mCherry and Luciferase-expressing AML cell lines (MOLM-14, OCI-AML-2, and OCI-AML-3) were intravenously engrafted into CD34+ humanized mice, derived from highly immunodeficient NCG mice engrafted with CD34+ HSCs from human cord blood. Tumor burden was monitored using in vivo bioluminescence, and tissue infiltration and immune system phenotype were characterized through flow cytometry.

Results

Results indicated successful engraftment of AML tumors and allowed comprehensive characterization of the preclinical tumor mouse model, including assessing bioluminescence to track tumor burden, disease progression, and survival rates in real-time. Further characterization in various tissues revealed the complete immune characteristics of the tumor model.

Conclusions

In conclusion, we have successfully established three AML cell lines in humanized mice, allowing for detailed analysis of tumor growth and tissue infiltration. Utilizing the HIS mice model, our research aims to enrich understanding of AML, paving the way for the development of novel therapies. The establishment of these models signifies a major step in leukemia research, potentially leading to improved treatment strategies and better patient outcomes.