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. 2023 Aug 26;37(10):2006–2016. doi: 10.1038/s41375-023-02010-y

Fig. 3. In vivo activity of 1B7/CD3 bispecific antibody (BsAb) in the REH-TSLPR cell line derived xenograft model.

Fig. 3

A Schematic of experimental design. Female NSG mice at 6–10 weeks old received a tail vein injection of 0.1 M REH-TSLPR human acute lymphoblastic leukemia (ALL) cells per mouse. Two weeks after tumor inoculation, 10 M PBMC/mouse were intravenously injected for humanization. Three days after the PBMC injection, mice were randomized into control and treatment groups. Mice were either treated with vehicle control or 1B7/CD3 at different doses at indicated time points. Tumor burden was assessed by imaging using IVIS (PerkinElmer). B Imaging (top) and radiance plot (bottom) monitoring tumor growth in donor 296 humanized mice (Donor PBMC-296) treated with control (PBS) or 1B7/CD3 (1 mg/kg) at indicated time points. Data are shown as mean ± SD. C Imaging (top) and radiance plot (bottom) monitoring tumor growth in donor 879 humanized mice (Donor PBMC-879) treated with control (PBS) or 1B7/CD3 at doses of 1, 0.1, 0.05, and 0.01 mg/kg at indicated time points. Data are shown as mean ± SD. D Tumor burden in the bone marrow (BM) from donor 879 humanized mice. BM was harvested 24 h. after the last dosing. Data are shown as mean ± SD; *p < 0.05 compared with control. E Percentage of CD3+T cells in the blood from donor 879 humanized mice collected at 24 h. post second dosing. Data was analyzed by GraphPad Prism 9 and shown as mean ± SD; **p < 0.01 compared with control. F Dynamic shifting of the T cell phenotype as donor 879 humanized mice receive repeated dosing of 1B7/CD3 treatment or control. Blood was collected at week two and week three post treatment. TSCM, stem memory T cells (CD45RO–CD62L+); TCM, memory T cells (CD45RO+CD62L) +; TEM, effector memory T cells (CD45RO+CD62L–); TEMRA, effector memory cells re-expressing CD45RA T cells (CD45RA+CD62L–).