Matsushita, M.; Saito, S.; Yokoe, S.; Ichikawa, D.; Hattori, Y. Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy. Vaccines2020, 8, 579.
Matsushita, M.; Saito, S.; Yokoe, S.; Ichikawa, D.; Hattori, Y. Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy. Vaccines 2020, 8, 579.
Matsushita, M.; Saito, S.; Yokoe, S.; Ichikawa, D.; Hattori, Y. Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy. Vaccines2020, 8, 579.
Matsushita, M.; Saito, S.; Yokoe, S.; Ichikawa, D.; Hattori, Y. Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy. Vaccines 2020, 8, 579.
Abstract
Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by RT-PCR using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.
Keywords
myeloma; antigen; demethylating agents
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
