The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses

Krista Pennington, Quyen D. Chu, David T. Curiel, Benjamin D.L. Li, James Michael Mathis

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Background. Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods. Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results. Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. Conclusions. We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.

Original languageEnglish
Pages (from-to)270-275
Number of pages6
JournalJournal of Surgical Research
Volume163
Issue number2
DOIs
StatePublished - 1 Oct 2010

Fingerprint

Adenoviridae
Breast Neoplasms
Tropism
Virus Replication
Viruses
Infection
Oncolytic Viruses
Viral Genome
Virus Diseases
Virion
Real-Time Polymerase Chain Reaction
Microscopy
Neoplasms
Breast
Therapeutics
Cell Culture Techniques
Cell Count
Immunohistochemistry
Phenotype
Cell Line

Keywords

  • CAR
  • CD46
  • adenovirus
  • breast cancer
  • oncolytic
  • tissue slice model

Cite this

Pennington, Krista ; Chu, Quyen D. ; Curiel, David T. ; Li, Benjamin D.L. ; Mathis, James Michael. / The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses. In: Journal of Surgical Research. 2010 ; Vol. 163, No. 2. pp. 270-275.
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abstract = "Background. Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods. Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results. Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. Conclusions. We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.",
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The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses. / Pennington, Krista; Chu, Quyen D.; Curiel, David T.; Li, Benjamin D.L.; Mathis, James Michael.

In: Journal of Surgical Research, Vol. 163, No. 2, 01.10.2010, p. 270-275.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses

AU - Pennington, Krista

AU - Chu, Quyen D.

AU - Curiel, David T.

AU - Li, Benjamin D.L.

AU - Mathis, James Michael

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N2 - Background. Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods. Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results. Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. Conclusions. We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.

AB - Background. Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods. Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results. Infection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices. Conclusions. We have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.

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SN - 0022-4804

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