Abstract:
:The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2(+) immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2(+) MM cells. We identified a novel immunogenic HLA-A2-specific CS1(239-247) (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1(239-247) peptide-specific CD8(+) T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and γ-interferon (IFN-γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO(+) CCR7(-) /CD3(+) CD8(+) ) within CS1-CTL showed a higher level of CD107a degranulation and IFN-γ production as compared to effector cells (CD45RO(-) CCR7(-) /CD3(+) CD8(+) ) against HLA-A2(+) primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1(239-247) peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Bae J,Song W,Smith R,Daley J,Tai YT,Anderson KC,Munshi NCdoi
10.1111/j.1365-2141.2012.09111.xsubject
Has Abstractpub_date
2012-06-01 00:00:00pages
687-701issue
6eissn
0007-1048issn
1365-2141journal_volume
157pub_type
杂志文章abstract::Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enabl...
journal_title:British journal of haematology
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abstract::FLT3-internal tandem duplication (ITD) mutations are heterogeneous with regards to length and proportion of DNA harbouring the mutation and the expression level of FLT3 also varies widely, however very little is known about the biological effects of these variables. We studied FLT3-associated biological parameters in ...
journal_title:British journal of haematology
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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abstract::Minimal residual disease (MRD) in acute myeloid leukaemia (AML) poses a major challenge due to drug insensitivity and high risk of relapse. Intensification of chemotherapy and stem cell transplantation are often pivoted on MRD status. Relapse rates are high even with the integration of first-generation FMS-like tyrosi...
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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