Cancer/testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in multiple myeloma (MM), exhibits tissue-restricted expression and is an independent negative prognostic factor for MM. We sought to characterize CT7 protein expression in the bone marrow (BM) of MM patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation (alloTCD-HSCT), and to examine the significance of CT7-specific cellular immune responses. We further aimed to determine CT7-derived immunogenic epitopes and their associated allelic restrictions. CT7 protein expression in neoplastic CD138+ plasma cells was evaluated by immunohistochemistry in BM biopsies from 10 patients. CT7 was present in 8/10 patients. Longitudinal analyses of 10 patients revealed an association between CT7 expression and prognosis. Longitudinal monitoring of CT7-specific T cells revealed an association between increased frequencies of CT7-specific T cells and reductions in specific myeloma markers. Epitope-specific reactivity to the nonamer FLAMLKNTV was detected by intracellular IFN-γ assay in peripheral blood (PB) and BM-derived T-cells from HLA-A*0201+ patients. Serial monitoring of PB CT7-specific T cell frequencies in 4 HLA-A*0201+ patients by HLA-A*0201-CT7(1087-1095) tetramer staining revealed an association with disease course. Phenotypic analyses revealed BM enrichment for central memory CT7- specific T cells, while effector memory cells dominated the PB. Together, these findings support the development of immunotherapeutic strategies that aim to enhance CT7-directed immune responses for the treatment of MM. -
- Received October 4, 2013.
- Revision received February 11, 2014.
- Accepted February 11, 2014.
- Copyright © 2014, American Association for Cancer Research.