Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck.

Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck. Research Abstract Details 

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Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck. Abstract Text:

Zeng B Zhu,J Michael Mathis,Sharmila K Makhija,Baogen Lu,Minghui Wang,Shaonin Ji,Angel A Rivera,Eben L Rosenthal,Gene P Siegal,David T Curiel,Zeng B Zhu,J Michael Mathis,Sharmila K Makhija,Baogen Lu,Minghui Wang,Shaonin Ji,Angel A Rivera,Eben L Rosenthal,Gene P Siegal,David T Curiel,

Conventional cancer treatments are not adequate for the majority of most patients stricken with squamous cell carcinomas of the head and neck (SCCHN). Conditionally replicating adenoviruses (CRAds) represent a promising new modality for treating of neoplastic diseases, including SCCHN. Specifically, CRAd agents infect tumor cells and selectively replicate within them, thus causing their death while sparing surrounding normal cells in the host. Oncolysis results from the replicative life cycle of the virus, which lyses infected tumor cells and releases viral progeny for propagation of infection and resultant lysis of neighboring cancer cells, sparing normal host cells. However, to date there have been two main limitations to successful clinical application of these CRAd agents: poor infectivity and poor tumor specificity. Here we report the construction of a CRAd agent, CRAd-CXCR4.F5/3, in which the adenovirus E1 gene is driven by a tumor-specific CXCR4 promoter, and the viral infectivity is enhanced by a fiber modification, F5/3, containing an Ad3 knob chimeric fiber protein. As expected, this agent improved both of the viral infectivity and tumor specificity as evaluated in established SCCHN tumor cell lines and in primary tumor tissues from multiple patients. As an added benefit, the activity of the CXCR4 promoter was low in human liver as described previously. Based on these data, the CRAd-CXCR4.F5/3 is a promising novel CRAd agent for SCCHN targeting with low host toxicity.

Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck. Publishing Authors By Initials

ZB Zhu,JM Mathis,SK Makhija,B Lu,M Wang,S Ji,AA Rivera,EL Rosenthal,GP Siegal,DT Curiel,ZB Zhu,JM Mathis,SK Makhija,B Lu,M Wang,S Ji,AA Rivera,EL Rosenthal,GP Siegal,DT Curiel,

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Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: International journal of oncology

VOLUME: 31

Page Numbers: 1213-22

Journal Abbreviation: Int. J. Oncol.

ISSN: 1019-6439

DAY: 3

MONTH: Nov

YEAR: 2007

Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck. Information

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LANGUAGE: eng

NlmUniqueID: 9306042

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Grant and Affiliation Information for Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck.

AFFILIATION: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Country: Greece

AGENCY: United States NCI

GRANT: R41 CA 114921

ACRONYM: CA

MEDLINETA: Int J Oncol

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