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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2233. This Article Full Text (PDF) All Versions of this Article: 2002-07-2233v1 101/4/1645    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 Luznik, L. Articles by Fuchs, E. J Search for Related Content PubMed PubMed Citation Articles by Luznik, L. Articles by Fuchs, E. J Social Bookmarking                   What's this? Submitted July 29, 2002 Accepted October 1, 2002 Successful therapy of metastatic cancer using tumor vaccines in mixed allogeneic bone marrow chimeras Leo Luznik, Jill E Slansky, Sanju Jalla, Ivan Borrello, Hyam I Levitsky, Drew M Pardoll, and Ephraim J Fuchs* Department of Oncology, Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO, USA * Corresponding author; email: fuchsep{at}jhmi.edu. A frequent outcome of allogeneic stem cell transplantation (alloSCT) in the treatment of leukemia is the destruction of the host hematolymphoid compartment, and thus the malignancy, through the combined action of high dose chemoradiotherapy and a T cell-mediated graft-versus host-effect. Unfortunately, alloSCT is frequently limited by toxicity, including graft-versus-host disease (GVHD), and has not been successful in the treatment of tumors derived from solid organs. Here we report a novel cooperation between host and donor T cells in the response to a tumor cell vaccine given after a non-myeloablative allogeneic stem cell transplantation (NST) protocol that achieves stable mixed bone marrow chimerism. Treatment of animals with NST, post-transplant donor lymphocyte infusions (DLI), and a vaccine, comprising irradiated autologous tumor cells mixed with a GM-CSF producing bystander line, results in potent and specific anti-tumor immunity. This combined modality immunotherapy, administered after surgical removal of the primary tumor, cured metastatic mammary cancer in the majority of animals without inducing GVHD. Cured animals contained tumor-specific T cells of both host and donor origin, but immunodeficient hosts could not be cured by NST, DLI, and vaccine administration. Thus, transfer of allogeneic donor T cells may help break functional tolerance of a host immune system to a solid tumor, thereby providing a rationale for the generation of mixed hematopoietic chimerism by NST prior to tumor cell vaccination. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Filatenkov, A. M. S. Muller, W. W.-L. Tseng, S. Dejbakhsh-Jones, D. Winer, R. Luong, J. A. Shizuru, E. G. Engleman, and S. Strober Ineffective Vaccination against Solid Tumors Can Be Enhanced by Hematopoietic Cell Transplantation J. Immunol., December 1, 2009; 183(11): 7196 - 7203. [Abstract] [Full Text] [PDF] M. G. LaCelle, S. M. Jensen, and B. A. Fox Partial CD4 Depletion Reduces Regulatory T Cells Induced by Multiple Vaccinations and Restores Therapeutic Efficacy Clin. Cancer Res., November 15, 2009; 15(22): 6881 - 6890. [Abstract] [Full Text] [PDF] S. Wada, K. Yoshimura, E. L. Hipkiss, T. J. Harris, H.-R. 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