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KMID : 0360320010330060500
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Journal of Korean Cancer Research Association
2001 Volume.33 No. 6 p.500 ~ p.511
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Evaluation of E1B - mutant Replicating Adenoviruses for Cancer Gene Therapy
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예병일/Byung Il Yeh
한동표/손준형/윤준호/이현우/장세진/공인덕/김현원/최종환/Dong Pyou Han/Joon Hyung Sohn/Joon Ho Yoon/Hyun Woo Lee/Sei Jin Chang/In Deok Kong/Hyun Won Kim/Jong Whan Choi
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Abstract
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PURPOSE:
Gene-attenuated replication-competent adenoviruses are emerging as a promising new modality for the treatment of cancer. In an effort to continually improve upon cancer gene therapy, we have modified gene- attenuated replication-competent adenoviruses so as to cause them to replicate efficiently and lyse the infected cancer cells more effectively.
MATERIALS AND METHODS:
We modified the E1 region of the adenovirus (Ad) systematically, generating Ad-deltaE1B19, Ad-deltaE1B55, Ad-deltaE1B19/55, and Ad-WT. The cytopathic effects (CPE) and viral replication of these four gene modified adenoviruses were compared, and the morphology and DNA fragmentation of the infected cells was evaluated.
RESULTS:
Among the constructed adenoviruses, E1B 19kD-inactivated adenovirus (Ad-deltaE1B19) was the most potent, inducing the largest-sized plaques and markedCPE. Moreover, cells infected with Ad-deltaE1B19 showed complete cell lysis with disintegrated cellular structure whereas cells infected with Ad-WT maintained intact cellular and nuclear membrane with properly structured organelles. TUNEL assay was also used to monitor DNA integrity, and a more profound induction of apoptosis was observed in the Ad-deltaE1B19 infected cells in comparison to wild type adenovirus infected cells.
CONCLUSION:
We demonstrate that the inactivation of the E1B19kD gene in a replicating adenovirus leads to increased CPE, rapid viral release, improved cell-to-cell viral spread and increased induction of apoptosis.
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KEYWORD
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Cancer gene therapy, Replication-competent adenovirus, Apoptosis,
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