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ID 50734
フルテキストURL
著者
Nobuoka, Daisuke Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Yoshikawa, Toshiaki Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Takahashi, Mari Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Iwama, Tatsuaki Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Horie, Kazutaka Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Shimomura, Manami Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Suzuki, Shiro Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Sakemura, Noriko Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Nakatsugawa, Munehide Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
Sadamori, Hiroshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Yagi, Takahito Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Fujiwara, Toshiyoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Nakatsura, Tetsuya Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
抄録
Antigen-specific cancer immunotherapy is a promising strategy for improving cancer treatment. Recently, many tumor-associated antigens and their epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the density of endogenously presented antigen-derived peptides on tumor cells is generally sparse, resulting in the inability of antigen-specific CTLs to work effectively. We hypothesize that increasing the density of an antigen-derived peptide would enhance antigen-specific cancer immunotherapy. Here, we demonstrated that intratumoral peptide injection leads to additional peptide loading onto major histocompatibility complex class I molecules of tumor cells, enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, human leukocyte antigen (HLA)-A*02:01-restricted glypican-3(144-152) (FVGEFFTDV) and cytomegalovirus(495-503) (NLVPMVATV) peptide-specific CTLs showed strong activity against all peptide-pulsed cell lines, regardless of whether the tumor cells expressed the antigen. In in vivo studies using immunodeficient mice, glypican-3(144-152) and cytomegalovirus(495-503) peptides injected into a solid mass were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of ovalbumin(257-264) peptide (SIINFEKL) was effective for tumor growth inhibition and survival against ovalbumin-negative tumors without adverse reactions. Moreover, we demonstrated an antigen-spreading effect that occurred after intratumoral peptide injection. Intratumoral peptide injection enhances tumor cell antigenicity and may be a useful option for improvement in antigen-specific cancer immunotherapy against solid tumors.
キーワード
Intratumoral peptide injection
Antigen
Immunotherapy
Cytotoxic T lymphocyte
発行日
2013-04
出版物タイトル
Cancer Immunology, Immunotherapy
62巻
4号
開始ページ
639
終了ページ
652
ISSN
0340-7004
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1007/s00262-012-1366-6
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/50734
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT