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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3865-3870. Prepublished online as a Blood First Edition Paper on August 10, 2006; DOI 10.1182/blood-2006-04-014415. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-014415v1 108/12/3865    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Zirlik, K. M. Articles by Gribben, J. G. Search for Related Content PubMed PubMed Citation Articles by Zirlik, K. M. Articles by Gribben, J. G. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide Katja Mauerer Zirlik, David Zahrieh, Donna Neuberg, and John G. Gribben From the Departments of Medical Oncology and Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Department of Hematology/Oncology, Freiburg University Medical Center, Germany. Heteroclitic peptide modifications increase immunogenicity, allowing generation of cytotoxic T lymphocytes (CTLs) against weakly immunogenic tumor-associated antigens (TAAs). A critical issue is whether T cells generated against heteroclitic peptides retain the ability to recognize and kill tumor cells expressing the original weak TAAs, and whether there is a lower threshold of binding affinity of the native peptides, below which such CTLs can still kill primary tumor cells. To examine this we used a model examining the ability of native and heteroclitic immunoglobulin (Ig)–derived peptides to generate CTLs that can kill chronic lymphocytic leukemia (CLL) cells. We demonstrate that CTLs generated against heteroclitic peptides have enhanced killing of CD40-activated B cells pulsed with either heteroclitic (P < .001) or native peptide (P = .04) and primary CLL cells (P = .01). The novel finding reported here is that the rate-limiting factor appears to be the ability to generate CTLs and that once generated, CTL lysis of primary tumor cells is independent of the binding affinity of the native peptide. These findings have implications for vaccination strategies in malignancies and are currently being further examined in vivo in murine models. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Papewalis, M. Wuttke, J. Seissler, Y. Meyer, C. Kessler, B. Jacobs, E. Ullrich, H. S. Willenberg, S. Schinner, T. Baehring, et al. Dendritic Cell Vaccination with Xenogenic Polypeptide Hormone Induces Tumor Rejection in Neuroendocrine Cancer Clin. Cancer Res., July 1, 2008; 14(13): 4298 - 4305. [Abstract] [Full Text] [PDF] A. P. Kater, M. H. J. van Oers, and T. J. Kipps Cellular immune therapy for chronic lymphocytic leukemia Blood, October 15, 2007; 110(8): 2811 - 2818. [Abstract] [Full Text] [PDF]

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