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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1681-1688. Prepublished online as a Blood First Edition Paper on November 13, 2008; DOI 10.1182/blood-2007-09-114157. This Article Full Text (PDF) All Versions of this Article: blood-2007-09-114157v1 113/8/1681    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 Fonseca, C. Articles by Dranoff, G. Search for Related Content PubMed PubMed Citation Articles by Fonseca, C. Articles by Dranoff, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2007 Accepted November 4, 2008 Protein disulfide isomerases are antibody targets during immune-mediated tumor destruction Catia Fonseca, Robert Soiffer, Vincent Ho, Matthew Vanneman, Masahisa Jinushi, Jerome Ritz, Donna Neuberg, Richard Stone, Dan DeAngelo, and Glenn Dranoff* Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States * Corresponding author; email: glenn_dranoff{at}dfci.harvard.edu. The identification of cancer antigens that contribute to transformation and are linked with immune-mediated tumor destruction is an important goal for immunotherapy. Towards this end, we screened a murine renal cell carcinoma cDNA expression library with sera from mice vaccinated with irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Multiple non-mutated, over-expressed proteins that function in tumor cell migration, protein/nucleic acid homeostasis, metabolism, and stress responses were detected. Among these, the most frequently recognized clone was protein disulfide isomerase (PDI). High titer antibodies to human PDI were similarly induced in an acute myeloid leukemia patient who achieved a complete response following vaccination with irradiated, autologous GM-CSF secreting tumor cells in the setting of non-myeloablative allogeneic bone marrow transplantation. Moreover, ERp5, a closely related disulfide isomerase involved in MHC class I chain-related protein A (MICA) shedding, also evoked potent humoral reactions in diverse solid and hematologic malignancy patients who responded to GM-CSF secreting tumor cell vaccines or antibody blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Together, these findings reveal the unexpected immunogenicity of protein disulfide isomerases and raise the possibility that these gene products might serve as targets for therapeutic monoclonal antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. T. Ho, M. Vanneman, H. Kim, T. Sasada, Y. J. Kang, M. Pasek, C. Cutler, J. Koreth, E. Alyea, S. Sarantopoulos, et al. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation PNAS, September 15, 2009; 106(37): 15825 - 15830. [Abstract] [Full Text] [PDF]

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