論文 - 詳細
| RRC ID | 64051 |
|---|---|
| 著者 | Nobuoka D, Yoshikawa T, Takahashi M, Iwama T, Horie K, Shimomura M, Suzuki S, Sakemura N, Nakatsugawa M, Sadamori H, Yagi T, Fujiwara T, Nakatsura T. |
| タイトル | Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
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-3144-152 (FVGEFFTDV) and cytomegalovirus495-503 (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-3144-152 and cytomegalovirus495-503 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 ovalbumin257-264 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. |
| 巻・号 | 62(4) |
| ページ | 639-52 |
| 公開日 | 2013-4-1 |
| DOI | 10.1007/s00262-012-1366-6 |
| PMID | 23143746 |
| PMC | PMC3624010 |
| MeSH | Animals Cell Line, Tumor Colonic Neoplasms / immunology Colonic Neoplasms / therapy Epitopes, T-Lymphocyte / immunology* Female HLA-A Antigens / immunology* Hep G2 Cells Humans Immunotherapy / methods* Injections, Intralesional Liver Neoplasms / immunology Liver Neoplasms / therapy Lymphoma / immunology Lymphoma / therapy Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Mice, Transgenic Peptide Fragments / administration & dosage* Peptide Fragments / immunology* T-Lymphocytes, Cytotoxic / immunology* |
| IF | 5.442 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | T2(RCB1932) |