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...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0326857 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 1932-6203 |