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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1844-1852. Prepublished online as a Blood First Edition Paper on June 10, 2008; DOI 10.1182/blood-2007-11-125492. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-11-125492v1 112/5/1844    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 Hambach, L. Articles by Goulmy, E. Search for Related Content PubMed PubMed Citation Articles by Hambach, L. Articles by Goulmy, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 29, 2007 Accepted May 3, 2008 Targeting a single mismatched minor histocompatibility antigen with tumor-restricted expression eradicates human solid tumors Lothar Hambach*, Marcel Vermeij, Andreas Buser, Zohara Aghai, Theodorus van der Kwast, and Els Goulmy Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands Erasmus Medical Center, Department of Pathology, Rotterdam, Netherlands * Corresponding author; email: l.w.h.hambach{at}lumc.nl. Regressions of metastatic solid tumors after allogeneic human leukocyte antigen (HLA)-matched stem-cell transplantation (SCT) are often associated with detrimental graft-versus-host-disease (GvHD). The graft-versus-host reaction of the HLA-matched donor is mainly directed against the multiple mismatched minor histocompatibility antigens (mHags) of the patient. mHags are strong HLA-restricted allo-antigens with differential tissue distribution. Ubiquitously expressed mHags are the prime in situ targets of GvHD. The mHag HA-1 is hematopoiesis-restricted, but displays additionally an aberrant expression on solid tumors. Thus, HA-1 might be an excellent target to boost the anti-solid tumor effect of allogeneic SCT without inducing severe GvHD. Here, we show that cytotoxic T-lymphocytes (CTLs) solely targeting the human mHag HA-1 are capable of eradicating three-dimensional human solid tumors in a highly mHag specific manner in vitro, accompanied by interferon-gamma release. In vivo, HA-1 specific CTLs distribute systemically and prevent human breast cancer metastases in immunodeficient mice. Moreover, HA-1 specific CTLs infiltrate and inhibit the progression of fully established metastases. Our study provides the first proof for the efficacy of a clinically applicable concept to exploit single mismatched mHags with hematopoiesis- and solid tumor-restricted expression for boosting the anti-solid tumor effect of allogeneic SCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Hambach, K.-W. Ling, J. Pool, Z. Aghai, E. Blokland, H. J. Tanke, J. A. Bruijn, H. Halfwerk, H. van Boven, B. Wieles, et al. Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy Blood, March 19, 2009; 113(12): 2715 - 2722. [Abstract] [Full Text] [PDF]

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