Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer

Xiong Li, Yan Ping Zhang, Hong Sup Kim, Kyung Hee Bae, Keith M. Stantz, Sang Jin Lee, Chaeyong Jung, Juan A. Jiménez, Thomas Gardner, Meei Huey Jeng, Chinghai Kao

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

PSES is a chimeric enhancer containing enhancer elements from prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) genes that are prevalently expressed in androgen-independent prostate cancers. PSES shows strong activity equivalent to cytomegalovirus (CMV) promoter, specifically in PSA/PSMA-positive prostate cancer cells, the major cell types in prostate cancer in the absence of androgen. We developed a recombinant adenovirus (AdE4P-SESE1a) by placing adenoviral E1a and E4 genes under the control of the bidirectional enhancer PSES and enhanced green fluorescent protein gene for the purpose of intratumoral virus tracking under the control of CMV promoter. Because of PSES being very weak in nonprostatic cells, including HEK293 and HER911 that are frequently used to produce recombinant adenovirus, AdE4PSESE1a can only be produced in the HER911E4 cell line which expresses both E1 and E4 genes. AdE4PSESE1a showed similar viral replication and tumor cell killing activities to wild-type adenovirus in PSA/PSMA-positive prostate cancer cells. The viral replication and tumor cell killing activities were dramatically attenuated in PSA/ PSMA-negative cells. To test whether AdE4PSESE1a could be used to target prostate tumors in vivo, CWR22rv s.c. tumors were induced in nude mice and treated with AdE4PSESE1a via intratumoral and tail vein injection. Compared to tumors treated with control virus, the growth of CWR22rv tumors was dramatically inhibited by AdE4PSESE1a via tail vein injection or intratumoral injection. These data show that adenoviral replication can be tightly controlled in a novel fashion by controlling adenoviral E1a and E4 genes simultaneously with a single enhancer.

Original languageEnglish
Pages (from-to)1941-1951
Number of pages11
JournalCancer Research
Volume65
Issue number5
DOIs
StatePublished - Mar 1 2005

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Adenoviridae
Genetic Therapy
Prostatic Neoplasms
Prostate-Specific Antigen
Gene Expression
Neoplasms
Genes
Cytomegalovirus
Androgens
Injections
Tail
Veins
Viruses
HEK293 Cells
Nude Mice
Prostate
Cell Line
human glutamate carboxypeptidase II
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer. / Li, Xiong; Zhang, Yan Ping; Kim, Hong Sup; Bae, Kyung Hee; Stantz, Keith M.; Lee, Sang Jin; Jung, Chaeyong; Jiménez, Juan A.; Gardner, Thomas; Jeng, Meei Huey; Kao, Chinghai.

In: Cancer Research, Vol. 65, No. 5, 01.03.2005, p. 1941-1951.

Research output: Contribution to journalArticle

Li, X, Zhang, YP, Kim, HS, Bae, KH, Stantz, KM, Lee, SJ, Jung, C, Jiménez, JA, Gardner, T, Jeng, MH & Kao, C 2005, 'Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer', Cancer Research, vol. 65, no. 5, pp. 1941-1951. https://doi.org/10.1158/0008-5472.CAN-04-3666
Li, Xiong ; Zhang, Yan Ping ; Kim, Hong Sup ; Bae, Kyung Hee ; Stantz, Keith M. ; Lee, Sang Jin ; Jung, Chaeyong ; Jiménez, Juan A. ; Gardner, Thomas ; Jeng, Meei Huey ; Kao, Chinghai. / Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer. In: Cancer Research. 2005 ; Vol. 65, No. 5. pp. 1941-1951.
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abstract = "PSES is a chimeric enhancer containing enhancer elements from prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) genes that are prevalently expressed in androgen-independent prostate cancers. PSES shows strong activity equivalent to cytomegalovirus (CMV) promoter, specifically in PSA/PSMA-positive prostate cancer cells, the major cell types in prostate cancer in the absence of androgen. We developed a recombinant adenovirus (AdE4P-SESE1a) by placing adenoviral E1a and E4 genes under the control of the bidirectional enhancer PSES and enhanced green fluorescent protein gene for the purpose of intratumoral virus tracking under the control of CMV promoter. Because of PSES being very weak in nonprostatic cells, including HEK293 and HER911 that are frequently used to produce recombinant adenovirus, AdE4PSESE1a can only be produced in the HER911E4 cell line which expresses both E1 and E4 genes. AdE4PSESE1a showed similar viral replication and tumor cell killing activities to wild-type adenovirus in PSA/PSMA-positive prostate cancer cells. The viral replication and tumor cell killing activities were dramatically attenuated in PSA/ PSMA-negative cells. To test whether AdE4PSESE1a could be used to target prostate tumors in vivo, CWR22rv s.c. tumors were induced in nude mice and treated with AdE4PSESE1a via intratumoral and tail vein injection. Compared to tumors treated with control virus, the growth of CWR22rv tumors was dramatically inhibited by AdE4PSESE1a via tail vein injection or intratumoral injection. These data show that adenoviral replication can be tightly controlled in a novel fashion by controlling adenoviral E1a and E4 genes simultaneously with a single enhancer.",
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AU - Stantz, Keith M.

AU - Lee, Sang Jin

AU - Jung, Chaeyong

AU - Jiménez, Juan A.

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AU - Kao, Chinghai

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