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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1876-1885. Prepublished online as a Blood First Edition Paper on June 30, 2008; DOI 10.1182/blood-2008-04-150045. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-150045v1 112/5/1876    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 Quintarelli, C. Articles by Savoldo, B. Search for Related Content PubMed PubMed Citation Articles by Quintarelli, C. Articles by Savoldo, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2008 Accepted June 16, 2008 Cytotoxic T lymphocytes directed to the Preferentially Expressed Antigen of Melanoma (PRAME) target chronic myeloid leukemia Concetta Quintarelli, Gianpietro Dotti, Biagio De Angelis, Valentina Hoyos, Martha Mims, Luigia Luciano, Helen E Heslop, Cliona M Rooney, Fabrizio Pane, and Barbara Savoldo* Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, United States Department of Immunology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, United States Department of Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, United States Hematology Unit, CEINGE-Biotecnologie Avanzate, University of Naples Federico II, Naples, Italy Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, United States Department of Molecular Virology and Microbiology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, United States * Corresponding author; email: bsavoldo{at}bcm.tmc.edu. The cancer testis antigen (CTA) "Preferentially Expressed Antigen of Melanoma" (PRAME) is overexpressed in many hematological malignancies, including Chronic Myeloid Leukemia (CML). The sensitivity of CML to donor lymphocyte infusion after allogeneic stem cell transplantation suggests this tumor can be highly susceptible to cellular immunotherapy targeted to tumor associated antigens. We therefore tested whether functional PRAME-specific cytotoxic T lymphocytes (PRAME-CTLs) could be generated and expanded from healthy donors and CML patients, or whether the limited immunogenicity of this CTA coupled with tumor-associated-anergy would preclude this approach. Using optimized culture conditions and HLA-A*02 restricted PRAME-peptides we have consistently generated PRAME-CTLs from 8/9 healthy donors and 5/6 CML patients. These CTLs released IFN in response to PRAME peptides (between 113±8 and 795±23 SFC/105 T cells) and lysed PRAME-peptide loaded cells (45±19% at an E:T ratio of 20:1) in an MHC-restricted fashion. Importantly, these CTLs recognized and had cytotoxic activity against HLA-A*02+/PRAME+ tumor cell lines, and could recognize and respond to primary CML cells. PRAME-CTLs were generated almost exclusively from the naive T-cell compartment and clonal analysis showed these cells could have high TCR-peptide avidity. PRAME-CTLs or vaccines may thus be of value for patients with CML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. G. Oehler, K. A. Guthrie, C. L. Cummings, K. Sabo, B. L. Wood, T. Gooley, T. Yang, M. T. Epping, Y. Shou, E. Pogosova-Agadjanyan, et al. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells Blood, October 8, 2009; 114(15): 3299 - 3308. [Abstract] [Full Text] [PDF] P. J. Hanley, C. R. Y. Cruz, B. Savoldo, A. M. Leen, M. Stanojevic, M. Khalil, W. Decker, J. J. Molldrem, H. Liu, A. P. Gee, et al. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes Blood, August 27, 2009; 114(9): 1958 - 1967. [Abstract] [Full Text] [PDF] K. Rezvani, A. S. M. Yong, A. Tawab, B. Jafarpour, R. Eniafe, S. Mielke, B. N. Savani, K. Keyvanfar, Y. Li, R. Kurlander, et al. Ex vivo characterization of polyclonal memory CD8+ T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia Blood, March 5, 2009; 113(10): 2245 - 2255. [Abstract] [Full Text] [PDF]

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