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Targeting Primary Human Ph+ B-Cell Precursor Leukemia-Engrafted SCID Mice Using Radiolabeled Anti-CD19 Monoclonal Antibodies

Paul Mitchell, MBBS1, Fook-Thean Lee, PhD2, Cathrine Hall, BSc2, Angela Rigopoulos, MSc2, Fiona E. Smyth, BSc2, Anne-Marie Hekman, PhD3, Gijs M. van Schijndel, PhD4, Ray Powles, PhD5, Martin W. Brechbiel, PhD6 and Andrew M. Scott, MD2,7

1 Ludwig Medical Oncology Unit, Ludwig Institute For Cancer Research, Melbourne Tumour Biology Branch, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia
2 Tumour Targeting Program, Ludwig Institute For Cancer Research, Melbourne Tumour Biology Branch, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia
3 Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
4 Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands
5 Leukemia Unit, Royal Marsden Hospital, Surrey, United Kingdom
6 Radioimmune and Inorganic Chemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
7 Department of Nuclear Medicine and Centre for PET, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia



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  		FIGURE 1. Histologic analysis of spleen obtained from SCID mouse engrafted with primary Ph+ ALL cells. Photomicrographs (x5) of hematoxylin- and eosin-stained splenic section (A) show extensive infiltration of leukemia cells expressing CD19 antigen (B). (C and D) Corresponding sections (x25) demonstrate lack of tissue architecture due to leukemia infiltration. When isotype control antibody was used, no staining was observed (data not shown).

 


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  		FIGURE 2. Whole-body gamma-camera images at 24, 48, and 72 h after injection. 111In-CHX-A''-DTPA CLB-CD19 for control SCID mice shows activity associated with blood pool (top row) and ALL-engrafted mice with spleen infiltrates (bottom row).

 


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  		FIGURE 3. Flow cytometric analysis of blood collected at various time points from SCID mice injected intravenously with 20 x 106 Ph+ ALL cells on day 0. Groups of mice (n = 8) were treated intravenously with CLB-CD19 antibody (A) or saline vehicle (B) on day 26. The mean ± SD proportion of human (open bars) and murine (hatched bars) cells expressing human or murine CD45, respectively, was expressed as percentage of total CD45+ white blood cells at each time point.

 




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