論文 - 詳細
| RRC ID | 65073 |
|---|---|
| 著者 | Yasunaga M, Manabe S, Matsumura Y. |
| タイトル | Immunoregulation by IL-7R-targeting antibody-drug conjugates: overcoming steroid-resistance in cancer and autoimmune disease. |
| ジャーナル | Sci Rep |
| Abstract |
Steroid-resistance is a common complication in the treatment of malignancies and autoimmune diseases. IL-7/IL-7R signaling, which regulates lymphocyte growth and survival, has been implicated in the development of malignancies and autoimmune diseases. However, the biological significance of IL-7/IL-7R signaling in steroid treatment is poorly understood. Here, we identified a novel relationship between IL-7R signaling and steroid-resistance, and showed that an anti-IL-7R antibody conjugated with SN-38 (A7R-ADC-SN-38) has strong anti-tumor effects against both parental and steroid-resistant malignant cells. Furthermore, inflammation in the mouse autoimmune arthritis model was suppressed to greater extent by A7R-ADC conjugated to MMAE than by A7R-ADC-SN-38. Given that an increased proportion of IL-7R-positive cells is a common mechanism underlying the pathogenesis of autoimmunity, we found that specific depletion of this cell population abrogated the progression of disease. This suggests that the cytotoxicity and immunosuppressive capacity of A7R-ADC could be modulated to treat specific malignancies or autoimmune diseases through the introduction of different payloads, and represents a novel alternative to steroid therapy. |
| 巻・号 | 7(1) |
| ページ | 10735 |
| 公開日 | 2017-9-6 |
| DOI | 10.1038/s41598-017-11255-4 |
| PII | 10.1038/s41598-017-11255-4 |
| PMID | 28878234 |
| PMC | PMC5587554 |
| MeSH | Animals Antibody-Dependent Cell Cytotoxicity Antineoplastic Agents, Immunological / pharmacology* Autoimmune Diseases / drug therapy Autoimmune Diseases / immunology Autoimmune Diseases / metabolism Autoimmune Diseases / pathology Disease Models, Animal Disease Progression Drug Resistance, Neoplasm / drug effects Female Gene Knockdown Techniques Humans Immunoconjugates / chemistry Immunoconjugates / pharmacology* Immunomodulation / drug effects* Mice Neoplasm Metastasis Neoplasms / drug therapy Neoplasms / immunology Neoplasms / metabolism Neoplasms / pathology Receptors, Interleukin-7 / antagonists & inhibitors* Receptors, Interleukin-7 / metabolism Signal Transduction Steroids / pharmacology Xenograft Model Antitumor Assays |
| IF | 3.998 |
| 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 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | NALM-6(RCB1933) PK45H(RCB1973) LC-2/ad(RCB0440) |