Medical College of Wisconsin
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Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein. Cancer Gene Ther 2003 Mar;10(3):193-200

Date

03/15/2003

Pubmed ID

12637940

DOI

10.1038/sj.cgt.7700555

Scopus ID

2-s2.0-0037345702   39 Citations

Abstract

We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and spread of virus from cell to cell, and thus its overexpression increases the oncolytic activity of the vectors. KD1 and KD3 contain mutations in the Ad5 E1A gene that knock out binding of the E1A proteins to cellular p300/CBP and pRB; these mutations allow KD1 and KD3 to grow well in cancer cells but not in normal cells. VRX-007 has wild-type E1A. Here we report that radiation increases the oncolytic activity of KD1, KD3, and VRX-007. This increased activity was observed in cultured cells, and it was not because of radiation-induced replication of the vectors. The combination of radiation plus KD3 suppressed the growth of A549 lung adenocarcinoma xenografts in nude mice more efficiently than radiation alone or KD3 alone. The combination of ADP-overexpressing vectors and radiation may have potential in treating cancer.

Author List

Toth K, Tarakanova V, Doronin K, Ward P, Kuppuswamy M, Locke JE, Dawson JE, Kim HJ, Wold WS

Author

Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenoviridae
Adenovirus E3 Proteins
Animals
Cell Line, Tumor
Combined Modality Therapy
Dose-Response Relationship, Radiation
Female
Genetic Therapy
Genetic Vectors
Humans
Lung Neoplasms
Mice
Mice, Nude
Neoplasms, Experimental
Xenograft Model Antitumor Assays
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a