Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice.
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 me...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0326857 |
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| author | Masahisa Hemmi Midori Yamashita Yoshiko Shimizu Shinsuke Nakao |
| author_facet | Masahisa Hemmi Midori Yamashita Yoshiko Shimizu Shinsuke Nakao |
| author_sort | Masahisa Hemmi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8bc0cb1873bc4b1b94eabfd647cb92e6 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8bc0cb1873bc4b1b94eabfd647cb92e62025-08-20T03:16:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032685710.1371/journal.pone.0326857Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice.Masahisa HemmiMidori YamashitaYoshiko ShimizuShinsuke NakaoOncolytic 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.https://doi.org/10.1371/journal.pone.0326857 |
| spellingShingle | Masahisa Hemmi Midori Yamashita Yoshiko Shimizu Shinsuke Nakao Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. PLoS ONE |
| title | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| title_full | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| title_fullStr | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| title_full_unstemmed | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| title_short | Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice. |
| title_sort | neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human cd46 transgenic mice |
| url | https://doi.org/10.1371/journal.pone.0326857 |
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