PRO 140 Monoclonal Antibody to CCR5 Prevents Acute Xenogeneic Graft-versus-Host Disease in NOD-scid IL-2Rynull Mice Denis R. Burger, Yvonne Parker, Kathryn.

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PRO 140 Monoclonal Antibody to CCR5 Prevents Acute Xenogeneic Graft-versus-Host Disease in NOD-scid IL-2Rynull Mice Denis R. Burger, Yvonne Parker, Kathryn Guinta, Daniel Lindner Biology of Blood and Marrow Transplantation Volume 24, Issue 2, Pages 260-266 (February 2018) DOI: 10.1016/j.bbmt.2017.10.041 Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Effect of PRO 140 on xeno-GVHD in NSG mice, PRO 140 2.0-mg dosing schedule. On day –1 male NSG mice received 2.25 cGy total body irradiation. On day 0 mice received 107 fresh Ficoll-Hypaque–purified normal human BM cells (male donor) i.v. via tail vein. Control mice received normal human IgG. On day 1 mice received 2.0 mg PRO 140 i.p. Eight mice per group; 2-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Effect of PRO 140 on xeno-GVHD in NSG mice, PRO 140 .2-mg dosing schedule. On day –1 male NSG mice received 2.25 cGy total body irradiation. On day 0 mice received 107 fresh Ficoll-Hypaque–purified normal human BM cells (male donor) i.v. via tail vein. Control mice received normal human IgG. On day 1 mice received .2 mg PRO 140 i.p. Eight mice per group; 2-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Effect of PRO 140 on xeno-GVHD in NSG mice. Flow cytometry analysis of engrafted human cells in PB from PRO 140 dosed i.p. twice a week started on day 1. PB (100 µL) was drawn on the days indicated from the saphenous vein into heparinized tubes. There were 8 animals per group, and experiments were performed twice. (A and C) High-dose experiment. (B and D) Low-dose experiment. Two-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Effect of PRO 140 on xeno-GVHD in NSG mice. Flow cytometry analysis of engrafted human cells in PB from PRO 140 dosed i.p. twice a week started on day 1. PB (100 µL) was drawn on day 54 from the saphenous vein into heparinized tubes. There were 8 animals per group (2 experimental groups, control IgG and PRO 140). The top 3 panels are representative of a single mouse from the control IgG group. The bottom 3 panels are representative of a single mouse from the PRO 140 group. Asterisks next to the absolute cell counts indicate P < .05 between experimental groups of 8 mice. Two-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Engraftment of human BM in NSG mice. Flow cytometry, gated on WBCs, human donor and murine recipient cells before engraftment (top, left is donor BM and top, right is recipient PB) and a representative murine recipient of PRO 140 high-dose experiment at the time mice were killed, day 75 (bottom, left PB and right BM). Two-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Effect of PRO 140 on xeno-GVHD in NSG mice. Flow cytometry analysis of engrafted human cells in PB, SPL, and BM at the time mice were killed. Two-column fitting image in color. Biology of Blood and Marrow Transplantation 2018 24, 260-266DOI: (10.1016/j.bbmt.2017.10.041) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions