CELL INTELLIGENCE · 肿瘤细胞治疗研究

Accurate in vivo models that recapitulate both acute myeloid leukemia (AML) progression and human immune responses are essential for the preclinical testing of novel immunotherapies. In this study, we developed and validated a bioluminescent NSG-SGM3 PBMC-THP-1 xenograft model that does not require cytotoxic or irradiation preconditioning and allows simultaneous assessment of leukemia burden, human chimerism, and immune checkpoint expression. Based on six consecutive experiments, we established that GFP/Luc-THP-1 is the preferred clone for the NSG-SGM3 strain when co-transplanted with healthy donor peripheral blood mononuclear cells (PBMC). The model demonstrated reproducible engraftment with predominant leukemic accumulation in the spleen and liver and measurable bone marrow disease, as confirmed by histopathology and flow cytometry.

PBMC co-transplantation induced a graft-versus-tumor effect, reduced peripheral tumor load, and enabled evaluation of augmenting immune response therapies. The optimal time point for evaluating the effects of immune therapies was determined to be day 40 after the co-injection of THP-1 and PBMC cells.

Immune checkpoint molecules TIM-3 and PD-L1 were expressed in peripheral blood, bone marrow, spleen, and extramedullary lesions, supporting the model's suitability for checkpoint-targeted strategies. The model was validated by anti-CD33 CAR-T cells and to a multi-checkpoint inhibitor, showed a numerical reduction in bioluminescence and partial histological clearance.