Figure 5.
Anti–PD-1 efficacy in a humanized glBRCA2 PDAC PDX model. A, Preclinical illustration of humanized mouse model generation. CD34+ cells were isolated from umbilical cord blood by magnetic beads. Purity was validated by FACS analysis. CD34+ cells or PBS control was injected into 3- to 4-week-old sublethal irradiated NSG mice. Peripheral blood was obtained every 2 to 3 weeks, and human CD45 was assessed. On week 18, a PDX tumor chunk was subcutaneously transplanted to mice and treated with pembrolizumab (10 mg/kg; i.p.) or vehicle control. B, Average tumor volume in nonhumanized mice (blue); humanized control-treated (green) mice; and humanized/pembrolizumab-treated mice (red). C, Immune cell characterization: mouse CD45 (mCD45), human CD45 (hCD45), B cells (CD19), and T cells (CD3) in the blood, spleen, and bone marrow of all mice at study termination. D, IHC staining of tumors demonstrating T-cell infiltrate in the CD34+ engrafted mice. Created with BioRender.com.