دورية أكاديمية
Molecular retargeting of antibodies converts immune defense against oncolytic viruses into cancer immunotherapy
| العنوان: | Molecular retargeting of antibodies converts immune defense against oncolytic viruses into cancer immunotherapy |
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| المؤلفون: | Niemann, Julia, Woller, Norman, Brooks, Jennifer, Fleischmann-Mundt, Bettina, Martin, Nikolas T., Kloos, Arnold, Knocke, Sarah, Ernst, Amanda M., Manns, Michael P., Kubicka, Stefan, Wirth, Thomas C., Gerardy-Schahn, Rita, Kühnel, Florian |
| المصدر: | Nature Communications ; volume 10, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Virus-neutralizing antibodies are a severe obstacle in oncolytic virotherapy. Here, we present a strategy to convert this unfavorable immune response into an anticancer immunotherapy via molecular retargeting. Application of a bifunctional adapter harboring a tumor-specific ligand and the adenovirus hexon domain DE1 for engaging antiadenoviral antibodies, attenuates tumor growth and prolongs survival in adenovirus-immunized mice. The therapeutic benefit achieved by tumor retargeting of antiviral antibodies is largely due to NK cell-mediated triggering of tumor-directed CD8 T-cells. We further demonstrate that antibody-retargeting (Ab-retargeting) is a feasible method to sensitize tumors to PD-1 immune checkpoint blockade. In therapeutic settings, Ab-retargeting greatly improves the outcome of intratumor application of an oncolytic adenovirus and facilitates long-term survival in treated animals when combined with PD-1 checkpoint inhibition. Tumor-directed retargeting of preexisting or virotherapy-induced antiviral antibodies therefore represents a promising strategy to fully exploit the immunotherapeutic potential of oncolytic virotherapy and checkpoint inhibition. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-019-11137-5 |
| الإتاحة: | https://doi.org/10.1038/s41467-019-11137-5Test https://www.nature.com/articles/s41467-019-11137-5.pdfTest https://www.nature.com/articles/s41467-019-11137-5Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.C74EEF09 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-11137-5 |
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