SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-12-3867. This Article Full Text (PDF) All Versions of this Article: 2002-12-3867v1 101/12/5068    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bethge, W. A Articles by Sandmaier, B. M Search for Related Content PubMed PubMed Citation Articles by Bethge, W. A Articles by Sandmaier, B. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted December 20, 2002 Accepted February 11, 2003 Selective T-cell ablation with bismuth-213 labeled anti-TCR as nonmyeloablative conditioning for allogeneic canine marrow transplantation Wolfgang A Bethge, D S Wilbur, Rainer Storb, Donald K Hamlin, Erlinda B Santos, Martin W Brechbiel, Darrell R Fisher, and Brenda M Sandmaier* Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA Department of Radiation Oncology, University of Washington, Seattle, WA, USA National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Pacific Northwest National Laboratory, Richland, WA, USA * Corresponding author; email: bsandmai{at}fhcrc.org. Two major immunological barriers, the host-versus-graft (HVG) and graft-versus-host (GVH) reactions, have to be overcome for successful allogeneic hematopoietic cell transplantation. T-cells have been shown to be primarily involved in these barriers in the major histocompatibility complex identical setting. We therefore hypothesized that selective ablation of T-cells using radioimmunotherapy together with postgrafting immunosuppression would suffice to ensure stable allogeneic engraftment. We had described a canine model of nonmyeloablative marrow transplantation in which host immune reactions were impaired by a single dose of 200 cGy total body irradiation (TBI) and both GVH and residual HVG reactions controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Here, we substituted the -emitter bismuth-213 (213Bi) linked to a monoclonal antibody (mAb) against TCR, using the metal-binding chelate CHX-A"-DTPA, for 200 cGy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dose finding study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) 213Bi. The treatment was administered in 6 injections on days -3 and -2 followed by transplantation of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. The therapy was well tolerated except for elevations of transaminases which were transient in all but one of the dogs. No other organ toxicities or signs of graft-versus-host disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55% after >30 weeks follow up. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Additional alpha applications David A. Scheinberg Blood 2003 101: 4651. [Full Text] [PDF] This article has been cited by other articles: H. Nakamae, D. S. Wilbur, D. K. Hamlin, M. S. Thakar, E. B. Santos, D. R. Fisher, A. L. Kenoyer, J. M. Pagel, O. W. Press, R. Storb, et al. Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the {alpha}-Emitting Radionuclides Bismuth-213 or Astatine-211 Cancer Res., March 15, 2009; 69(6): 2408 - 2415. [Abstract] [Full Text] [PDF] J. S. Jaggi, S. V. Seshan, M. R. McDevitt, K. LaPerle, G. Sgouros, and D. A. Scheinberg Renal Tubulointerstitial Changes after Internal Irradiation with {alpha}-Particle-Emitting Actinium Daughters J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2677 - 2689. [Abstract] [Full Text] [PDF] J. Singh Jaggi, B. J. Kappel, M. R. McDevitt, G. Sgouros, C. D. Flombaum, C. Cabassa, and D. A. Scheinberg Efforts to Control the Errant Products of a Targeted In vivo Generator Cancer Res., June 1, 2005; 65(11): 4888 - 4895. [Abstract] [Full Text] [PDF] E. R. Nemecek, D. K. Hamlin, D. R. Fisher, K. A. Krohn, J. M. Pagel, F. R. Appelbaum, O. W. Press, and D. C. Matthews Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model Clin. Cancer Res., January 15, 2005; 11(2): 787 - 794. [Abstract] [Full Text] [PDF] D. A. Mulford, D. A. Scheinberg, and J. G. Jurcic The Promise of Targeted {alpha}-Particle Therapy J. Nucl. Med., January 1, 2005; 46(1_suppl): 199S - 204S. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020