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
Kaken ID
publons
researchmap
Yagi, Takahito
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Kaken ID
publons
researchmap
Fujiwara, Toshiyoshi
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
ORCID
Kaken ID
publons
researchmap
Nakatsura, Tetsuya
Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy
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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.
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キーワード | Intratumoral peptide injection
Antigen
Immunotherapy
Cytotoxic T lymphocyte
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発行日 | 2013-04
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出版物タイトル |
Cancer Immunology, Immunotherapy
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巻 | 62巻
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号 | 4号
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開始ページ | 639
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終了ページ | 652
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ISSN | 0340-7004
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1007/s00262-012-1366-6
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/50734
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言語 |
英語
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論文のバージョン | publisher
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査読 |
有り
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DOI | |
Web of Science KeyUT |