論文 - 詳細
| RRC ID | 74484 |
|---|---|
| 著者 | Fujii SI, Yamasaki S, Hanada K, Ueda S, Kawamura M, Shimizu K. |
| タイトル | Cancer immunotherapy using artificial adjuvant vector cells to deliver NY-ESO-1 antigen to dendritic cells in situ. |
| ジャーナル | Cancer Sci |
| Abstract |
NY-ESO-1 is a cancer/testis antigen expressed in various cancer types. However, the induction of NY-ESO-1-specific CTLs through vaccines is somewhat difficult. Thus, we developed a new type of artificial adjuvant vector cell (aAVC-NY-ESO-1) expressing a CD1d-NKT cell ligand complex and a tumor-associated antigen, NY-ESO-1. First, we determined the activation of invariant natural killer T (iNKT) and natural killer (NK) cell responses by aAVC-NY-ESO-1. We then showed that the NY-ESO-1-specific CTL response was successfully elicited through aAVC-NY-ESO-1 therapy. After injection of aAVC-NY-ESO-1, we found that dendritic cells (DCs) in situ expressed high levels of costimulatory molecules and produced interleukn-12 (IL-12), indicating that DCs undergo maturation in vivo. Furthermore, the NY-ESO-1 antigen from aAVC-NY-ESO-1 was delivered to the DCs in vivo, and it was presented on MHC class I molecules. The cross-presentation of the NY-ESO-1 antigen was absent in conventional DC-deficient mice, suggesting a host DC-mediated CTL response. Thus, this strategy helps generate sufficient CD8+ NY-ESO-1-specific CTLs along with iNKT and NK cell activation, resulting in a strong antitumor effect. Furthermore, we established a human DC-transferred NOD/Shi-scid/IL-2γcnull immunodeficient mouse model and showed that the NY-ESO-1 antigen from aAVC-NY-ESO-1 was cross-presented to antigen-specific CTLs through human DCs. Taken together, these data suggest that aAVC-NY-ESO-1 has potential for harnessing innate and adaptive immunity against NY-ESO-1-expressing malignancies. |
| 巻・号 | 113(3) |
| ページ | 864-874 |
| 公開日 | 2022-3-1 |
| DOI | 10.1111/cas.15259 |
| PMID | 34971473 |
| PMC | PMC8898705 |
| MeSH | Adjuvants, Immunologic / administration & dosage* Adjuvants, Immunologic / metabolism Animals Antigens, CD1d / immunology Antigens, CD1d / metabolism Antigens, Neoplasm / administration & dosage* Antigens, Neoplasm / immunology Antigens, Neoplasm / metabolism Cancer Vaccines / administration & dosage* Cancer Vaccines / immunology Cancer Vaccines / metabolism Cross-Priming Dendritic Cells / immunology* HEK293 Cells Humans Immunotherapy / methods* Membrane Proteins / administration & dosage* Membrane Proteins / immunology Membrane Proteins / metabolism Mice NIH 3T3 Cells Natural Killer T-Cells / immunology Neoplasms, Experimental / immunology Neoplasms, Experimental / therapy T-Lymphocytes, Cytotoxic / immunology |
| IF | 4.966 |
| 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 | 3 |
| 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 | NIH3T3 |