Flt-3L-Ig (hum/hum)

BRGSF mice (female, 21-22 weeks old, humanized with umbilical cord blood CD34+ cells)^[1]

10 μg per injection

i.p.; four times on days 0, 2, 4, and 7 (every 2-3 days)

Increased OKT3-induced serum levels of IL-2, CCL2, and CXCL10.
Enhanced OKT3-induced body weight loss, reaching a 13-15% reduction from baseline at 48h post-OKT3.
Induced a significant temperature drop, a ~4-6% reduction from baseline at 24h post-OKT3, an effect not seen in non-boosted mice.
Amplified OKT3-induced depletion of plasmacytoid dendritic cells (pDCs), conventional dendritic cells (cDCs), and monocytes/macrophages.
Enhanced OKT3-induced activation of pDCs, cDCs, and neutrophils, measured by increased percentages of CD86+, CD80+, and CD86+/CD80+ cells in these populations.
Increased absolute and relative numbers of human monocytes/macrophages, pDCs, and cDCs in bone marrow, spleen, and systemic circulation without inducing significant immune cell activation.\nEnabled detection of Blinatumomab-induced CRS features, including significant increases in serum levels of human TNF-α, IL-6, IFN-γ, CCL2, and CXCL10, and a sustained, significant reduction in body temperature at the 5 μg/kg Blinatumomab dose.\nEnabled detection of JNJ-induced CRS features, including dose-dependent increases in serum levels of human CCL5, CCL2, CXCL8, TNF-α, IL-1RA, and IL-10.
Caused significant depletion of monocytes/macrophages and cDCs at 48h post-JNJ injection.
Induced significant increases in the percentage of CD86+ activated monocytes/macrophages and cDCs at 24h post-JNJ injection (at the 20 mg/kg JNJ dose).