Cancer-testis antigen 7 expression and immune responses following allogeneic stem cell transplantation for multiple myeloma Journal Article

Authors: Tyler, E. M.; Jungbluth, A. A.; Gnjatic, S.; O'Reilly, R. J.; Koehne, G.
Article Title: Cancer-testis antigen 7 expression and immune responses following allogeneic stem cell transplantation for multiple myeloma
Abstract: Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in multiple myeloma, exhibits tissue-restricted expression, and is an independent negative prognostic factor for multiple myeloma. We sought to characterize CT7 protein expression in the bone marrow of patients with multiple myeloma 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 bone marrow biopsies from 10 patients. CT7 was present in 8 of 10 patients. Longitudinal analyses of the 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╬│ assay in peripheral blood (PB) and bone marrow-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 bone marrow 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 multiple myeloma.
Keywords: transplantation, homologous; clinical trial; disease course; cd8+ t lymphocyte; cd8-positive t-lymphocytes; metabolism; multiple myeloma; bone marrow; hematopoietic stem cell transplantation; tumor antigen; immunology; cellular immunity; antigens, neoplasm; disease progression; epitope; epitopes, t-lymphocyte; allotransplantation; hla a2 antigen; hla-a2 antigen; immunity, cellular; procedures; humans; human; ct7 antigen, human
Journal Title: Cancer Immunology Research
Volume: 2
Issue: 6
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2014-06-01
Start Page: 547
End Page: 558
Language: English
DOI: 10.1158/2326-6066.cir-13-0174
PUBMED: 24894092
PROVIDER: scopus
PMCID: PMC5705031
Notes: Export Date: 2 March 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Guenther Koehne
    192 Koehne
  2. Achim Jungbluth
    387 Jungbluth
  3. Richard O'Reilly
    602 O'Reilly
  4. Eleanor M Tyler
    9 Tyler