Targeted Tumor Cell Death Induced by Autologous Tumor-Specific T Lymphocyte Recognition of Wild-Type p53-Derived Peptides |
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Authors: | Hideo Tsurushima Yoshihiko Yoshii Kam W Leong Tadao Ohno |
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Institution: | (1) Faculty of Medicine, Department of Neuro Surgery, University of the Ryukyus, Okinawa, Japan;(2) RIKEN Cell Bank, RIKEN, The Institute of Physical and Chemical Research, Tsukuba Science City, Japan;(3) Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, MD, USA;(4) Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 3601a, Tsukuba Central 5th-2, Higashi 1-1-1, Ibaraki Tsukuba, 305-8565, Japan |
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Abstract: | Summary Autologous tumor-specific T lymphocyte (ATTL) lines were derived from the peripheral blood mononuclear cells (PBMC) of a healthy
volunteer with human leukocyte antigen (HLA) -A*0201. These lines were achieved using interleukins -1β, -2, -4, and -6 and
the p53-based peptide from the 264–272 sequence of the wild-type p53 protein with a strong affinity against HLA-A*0201.
;The frequencies of CD3+, CD4+, and CD8+ lymphocytes were 94–96%, 30–34%, and 69–74%, respectively. ATTLs killed most of the
T2 cells pulsed with p53-derived peptide, but not against the T2 cells non-pulsed or pulsed with an irrelevant peptide. ATTLs
also killed TKB-14 cells, which have been derived from human glioblastoma multiforme, and exhibited HLA-A*0201 molecule and
immunohistochemical accumulation of p53 protein. These cytotoxic activities were inhibited by anti-CD3, anti-CD8, and anti-class
I antibodies.
These findings suggested that these ATTL lines might include CTL populations, which could recognize p53-derived peptide on
HLA-A*0201 and the p53-based peptide may play as an antigen on HLA-A*0201. When tumor antigens would be more analyzed in the
future, ATTL could be induced without the primary-cultured cells from tumor tissue and could be applied for cancer therapy. |
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Keywords: | antigen presentation cytotoxic T lymphocyte glioblastoma multiforme p53-immunopeptide |
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