論文 - 詳細
| RRC ID | 85208 |
|---|---|
| 著者 | Hemmi M, Yamashita M, Shimizu Y, Nakao S. |
| タイトル | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| ジャーナル | PLoS One |
| Abstract |
Oncolytic viruses are a unique modality with multifaceted mechanisms of action for killing cancer cells and have been developed as a promising therapeutic approach in cancer treatment. The first-in-class agent, talimogene laherparepvec (T-VEC), has shown clinical benefit in patients with advanced melanoma. However, intratumoral administration of oncolytic viruses has several limitations which prevent use against a broader range of cancer types. Here, we propose a novel treatment strategy consisting of the intravenous administration of a genetically engineered oncolytic adenovirus type 11 (Ad11) mixed with anti-Ad11 neutralizing monoclonal antibodies. Ad11, which has minimum binding affinity to human erythrocytes, was modified to selectively replicate in cancer cells. New anti-Ad11 antibody clones were generated which inhibit binding between Ad11 fibers and their natural receptor, CD46. The neutralizing antibodies suppressed viral accumulation in the lungs by about 10-fold in human CD46-transgenic mice without loss of infectivity to cancer cells. Our findings are important in ensuring safe and efficient virus delivery following intravenous administration in humans and may expand treatment options. |
| 巻・号 | 20(6) |
| ページ | e0326857 |
| 公開日 | 2025-1-1 |
| DOI | 10.1371/journal.pone.0326857 |
| PII | PONE-D-24-49759 |
| PMID | 40561062 |
| PMC | PMC12193558 |
| MeSH | Adenoviridae* / genetics Adenoviridae* / immunology Administration, Intravenous Animals Antibodies, Monoclonal* / administration & dosage Antibodies, Monoclonal* / immunology Antibodies, Neutralizing* / administration & dosage Antibodies, Neutralizing* / immunology Antibodies, Neutralizing* / pharmacology Cell Line, Tumor Humans Membrane Cofactor Protein* / genetics Membrane Cofactor Protein* / metabolism Mice Mice, Transgenic Oncolytic Virotherapy* / methods Oncolytic Viruses* / genetics Oncolytic Viruses* / immunology Tissue Distribution |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 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 | MKN45(RCB1001) |