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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.
NEOPLASIA Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia1 Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston; 2 School of Biotechnological Sciences, University of Naples Federico II, Naples, Italy; 3 CEINGE-Biotecnologie Avanzate SCARL, Naples, Italy; Departments of4 Medicine and 5 Immunology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston; 6 Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples Federico II, Naples, Italy; 7 Hematology Unit, CEINGE-Biotecnologie Avanzate, Naples, Italy; and Departments of8 Pediatrics and 9 Molecular Virology and Microbiology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston
The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed in many hematologic 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
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| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
in response to PRAME peptides (between 113 ± 8 and 795 ± 23 spot forming cells/105 T cells) and lysed PRAME peptide–loaded cells (45 ± 19% at an effector:target [E:T] ratio of 20:1) in a 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 
βTCR-peptide avidity. PRAME CTLs or vaccines may thus be of value for patients with CML. 
