Abstract
Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. Here, we created a hybrid vesicular stomatitis/measles virus (VSV/MV) that harnesses the safety of oncolytic MV, the speed of VSV, and the tumor killing mechanisms of both viruses. Oncolytic MV targets CD46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. VSV spreads rapidly, directly lysing tumor cells, but is neurotoxic and loses oncolytic potency when neuroattenuated by conventional approaches. The hybrid VSV/MV lacks neurotoxicity, replicates rapidly with VSV kinetics, and selectively targets CD46 on tumor cells. Its in vivo performance in a myeloma xenograft model was substantially superior to either MV or widely used recombinant oncolytic VSV-M51.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1930-1937 |
| Number of pages | 8 |
| Journal | Molecular Therapy |
| Volume | 21 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2013 |
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ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
- Genetics
- Drug Discovery
- Pharmacology
Cite this
Amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread. / Ayala-Breton, Camilo; Suksanpaisan, Lukkana; Mader, Emily K.; Russell, Stephen J; Peng, Kah-Whye.
In: Molecular Therapy, Vol. 21, No. 10, 10.2013, p. 1930-1937.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread
AU - Ayala-Breton, Camilo
AU - Suksanpaisan, Lukkana
AU - Mader, Emily K.
AU - Russell, Stephen J
AU - Peng, Kah-Whye
PY - 2013/10
Y1 - 2013/10
N2 - Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. Here, we created a hybrid vesicular stomatitis/measles virus (VSV/MV) that harnesses the safety of oncolytic MV, the speed of VSV, and the tumor killing mechanisms of both viruses. Oncolytic MV targets CD46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. VSV spreads rapidly, directly lysing tumor cells, but is neurotoxic and loses oncolytic potency when neuroattenuated by conventional approaches. The hybrid VSV/MV lacks neurotoxicity, replicates rapidly with VSV kinetics, and selectively targets CD46 on tumor cells. Its in vivo performance in a myeloma xenograft model was substantially superior to either MV or widely used recombinant oncolytic VSV-M51.
AB - Oncolytic viruses are structurally and biologically diverse, spreading through tumors and killing them by various mechanisms and with different kinetics. Here, we created a hybrid vesicular stomatitis/measles virus (VSV/MV) that harnesses the safety of oncolytic MV, the speed of VSV, and the tumor killing mechanisms of both viruses. Oncolytic MV targets CD46 and kills by forcing infected cells to fuse with uninfected neighbors, but propagates slowly. VSV spreads rapidly, directly lysing tumor cells, but is neurotoxic and loses oncolytic potency when neuroattenuated by conventional approaches. The hybrid VSV/MV lacks neurotoxicity, replicates rapidly with VSV kinetics, and selectively targets CD46 on tumor cells. Its in vivo performance in a myeloma xenograft model was substantially superior to either MV or widely used recombinant oncolytic VSV-M51.
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UR - http://www.scopus.com/inward/citedby.url?scp=84885023559&partnerID=8YFLogxK
U2 - 10.1038/mt.2013.164
DO - 10.1038/mt.2013.164
M3 - Article
C2 - 23842448
AN - SCOPUS:84885023559
VL - 21
SP - 1930
EP - 1937
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 10
ER -