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Novel epitope evoking CD138 antigen‐specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders
Author(s) -
Bae Jooeun,
Tai YuTzu,
Anderson Kenneth C.,
Munshi Nikhil C.
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08850.x
Subject(s) - ctl* , cytotoxic t cell , antigen , epitope , immune system , cd8 , biology , immunology , t cell , cancer research , in vitro , biochemistry
Summary The development of an immunotherapeutic strategy targeting CD138 antigen could potentially represent a new treatment option for multiple myeloma (MM). This study evaluated the immune function of CD138 peptide‐specific cytotoxic T lymphocytes (CTL), generated ex vivo using an HLA‐A2‐specific CD138 epitope against MM cells. A novel immunogenic HLA‐A2‐specific CD138 260–268 (GLVGLIFAV) peptide was identified from the full‐length protein sequence of the CD138 antigen, which induced CTL specific to primary CD138 + MM cells. The peptide‐induced CD138‐CTL contained a high percentage of CD8 + activated/memory T cells with a low percentage of CD4 + T cell and naive CD8 + T cell subsets. The CTL displayed HLA‐A2‐restricted and CD138 antigen‐specific cytotoxicity against MM cell lines. In addition, CD138‐CTL demonstrated increased degranulation, proliferation and γ‐interferon secretion to HLA‐A2 + /CD138 + myeloma cells, but not HLA‐A2 − /CD138 + or HLA‐A2 + /CD138 − cells. The immune functional properties of the CD138‐CTL were also demonstrated using primary HLA‐A2 + /CD138 + cells isolated from myeloma patients. In conclusion, a novel immunogenic CD138 260–268 (GLVGLIFAV) peptide can induce antigen‐specific CTL, which might be useful for the treatment of MM patients with peptide‐based vaccine or cellular immunotherapy strategies.