Identification of a glioma antigen, GARC-1, using cytotoxic T lymphocytes induced by HSV cancer vaccine
✍ Scribed by Yukihiko Iizuka; Hidefumi Kojima; Tetsuji Kobata; Takeshi Kawase; Yutaka Kawakami; Masahiro Toda
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 505 KB
- Volume
- 118
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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.