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
03/15/2003Pubmed ID
12637940DOI
10.1038/sj.cgt.7700555Scopus ID
2-s2.0-0037345702 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
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 WSAuthor
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenoviridaeAdenovirus 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
