Mouse Anti-NOTCH1 Recombinant Antibody (clone OMP-52M51) (CAT#: HPAB-0078-YC)

Figure 1 Anti-Notch1 inhibits the growth of Notch1-driven T-ALL xenografts.

(a) Outline of treatment with anti-Notch1 (OMP-52M51) or control antibody (ctrl Ab; Rituximab). NOD/SCID mice (n=6 mice/group) were i.p. treated with anti-Notch1 Ab 2 days after i.v. injection of T-ALL cells (5 × 106 cells/mouse). Antibodies were subsequently administered at weekly intervals at 20 mg/Kg. Leukemia engraftment was tracked by serial blood drawings and flow cytometric analysis. (b) Measurement of circulating blasts by flow cytometry after first blood drawing, 9-11 days from the beginning of the experiment (left panel, top). The last blood drawing was obtained at killing, when initial signs of illness appeared in control mice (right panel, top). Quantification of leukemia cells in the spleen (left panel, bottom) and the BM (right panel, bottom) was carried out at killing. Statistically significant differences are indicated (*P<0.05; **P<0.001). Genetic status of the T-ALL xenografts: PDTALL8, 11, 12 and 19 were NOTCH1-mutated samples, whereas PDTALL13, 16 and 18 xenografts had wild-type Notch1 receptors. (c) Kaplan-Meier survival curves of leukemic mice (PDTALL12 and PDTALL19 xenografts) after treatment with anti-Notch1 or ctrl Ab.

Agnusdei, V., Minuzzo, S., Frasson, C., Grassi, A., Axelrod, F., Satyal, S.,... & Valtorta, S. (2014). Therapeutic antibody targeting of Notch1 in T-acute lymphoblastic leukemia xenografts. Leukemia, 28(2), 278.

Figure 2 Anti-Notch1 therapy increases apoptosis and reduces proliferation of T-ALL cells.

(a) At killing, levels of apoptotic leukemic cells in the spleen (left panel) and in the BM (right panel) of control and anti-Notch1-treated mice were measured by annexin V labeling and flow cytometry (n=6 mice/group). Statistically significant differences in the two groups of samples are indicated. (b) Analysis of PARP cleavage by western blot in three representative samples from the spleen (left panel) of PDTALL19 mice treated with either control Ab or anti-Notch1. MOLT-3 cells treated with the pro-apoptotic drug anisomycin (5 μM) for 90 (t1) or 210  min (t2) were used as positive control (right panel). (c) Evaluation of leukemic cell proliferation by flow cytometric analysis following staining with CD5 and Ki67 of T-ALL cells from the spleen or the BM of anti-Notch1-treated mice (*P<0.05, **P<0.001).

Agnusdei, V., Minuzzo, S., Frasson, C., Grassi, A., Axelrod, F., Satyal, S.,... & Valtorta, S. (2014). Therapeutic antibody targeting of Notch1 in T-acute lymphoblastic leukemia xenografts. Leukemia, 28(2), 278.