| RRC ID |
85208
|
| Author |
Hemmi M, Yamashita M, Shimizu Y, Nakao S.
|
| Title |
Neutralizing monoclonal antibodies improve biodistribution of intravenously administered oncolytic adenovirus in human CD46-transgenic mice.
|
| Journal |
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.
|
| Volume |
20(6)
|
| Pages |
e0326857
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001) |
