Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes

Cancer Science
Koichiro SuemoriM Yasukawa

Abstract

CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. In the present study, to clarify the feasibility of CML66-targeted cancer immunotherapy, we attempted to identify cytotoxic T lymphocyte (CTL) epitopes derived from CML66. An immunogenic CML66-derived epitope (amino acid residues 76-84; YYIDTLGRI) capable of inducing human leukocyte antigen (HLA)-A*2402-restricted CTL specific for this peptide was identified. CML66-derived peptide-specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA-A*2402-restricted fashion. Quantitative real-time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. CML66-specific CTL precursors were detected in the peripheral blood of patients with acute leukemia. These data indicate that the CML66-derived epitope identified in the present study is a new target antigen for cellular immunotherapy of human leukemia.

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Citations

May 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wandi ZhangCatherine J Wu
Sep 30, 2008·Blood·Toshiki OchiMasaki Yasukawa
Apr 25, 2009·British Journal of Haematology·Koichiro SuemoriMasaki Yasukawa
Apr 2, 2009·Cancer Control : Journal of the Moffitt Cancer Center·Javier Pinilla-IbarzJason A Dubovsky
Jul 8, 2020·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Bin HeZengwang Zhang

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