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Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine
Author(s) -
Iizuka Yukihiko,
Kojima Hidefumi,
Kobata Tetsuji,
Kawase Takeshi,
Kawakami Yutaka,
Toda Masahiro
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21432
Subject(s) - glioma , cytotoxic t cell , antigen , ctl* , immunotherapy , epitope , biology , virology , cancer research , herpes simplex virus , cancer immunotherapy , immunology , virus , immune system , cd8 , in vitro , biochemistry
Despite several ongoing clinical trials of immunotherapies against glioma, few glioma‐specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor‐specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H‐2D b ‐restricted CTL line, GCL‐1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL‐1, and a new gene encoding glioma antigen, GARC‐1, was isolated. Sequence analysis revealed that the GARC‐1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T‐cell epitope analysis revealed that the mutated peptide GARC‐1 77–85 (AALLNKLYA) but not the wild‐type peptide (AALLDKLYA), was recognized by GCL‐1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor‐specific CTLs and identifying tumor antigens. Furthermore, this GL261/GARC‐1 murine glioma model may be useful for the development of immunotherapy for brain tumors. © 2005 Wiley‐Liss, Inc.