Persistent replication of the modified chimeric adenovirus ONYX-015 in both Tumor and stromal cells from a patient with gall bladder carcinoma implants

Scott Wadler, Bo Yu, Jian You Tan, Ron Kaleya, Alla Rozenblit, Della F. Makower, Morris Edelman, Maureen Lane, Elizabath Hyjek, Marshall Horwitz

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicate preferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene, hexon, would demonstrate replication of virus in human tissues. Experimental Design: In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 × 1010 viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication. Results: In situ Reverse transcription -PCR was used to measure expression of hexon. Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins. Conclusions: Evidence for replication of hexon confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalClinical Cancer Research
Volume9
Issue number1 I
StatePublished - Jan 1 2003

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Stromal Cells
Adenoviridae
Urinary Bladder
Carcinoma
Neoplasms
Immunohistochemistry
Intralesional Injections
Viral Genes
Abdominal Wall
Viral Proteins
Virus Replication
ONYX015
Virion
Reverse Transcription
Cytoplasm
Research Design
Necrosis
Clinical Trials
Staining and Labeling
Viruses

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Persistent replication of the modified chimeric adenovirus ONYX-015 in both Tumor and stromal cells from a patient with gall bladder carcinoma implants. / Wadler, Scott; Yu, Bo; Tan, Jian You; Kaleya, Ron; Rozenblit, Alla; Makower, Della F.; Edelman, Morris; Lane, Maureen; Hyjek, Elizabath; Horwitz, Marshall.

In: Clinical Cancer Research, Vol. 9, No. 1 I, 01.01.2003, p. 33-43.

Research output: Contribution to journalArticle

Wadler, S, Yu, B, Tan, JY, Kaleya, R, Rozenblit, A, Makower, DF, Edelman, M, Lane, M, Hyjek, E & Horwitz, M 2003, 'Persistent replication of the modified chimeric adenovirus ONYX-015 in both Tumor and stromal cells from a patient with gall bladder carcinoma implants', Clinical Cancer Research, vol. 9, no. 1 I, pp. 33-43.
Wadler, Scott ; Yu, Bo ; Tan, Jian You ; Kaleya, Ron ; Rozenblit, Alla ; Makower, Della F. ; Edelman, Morris ; Lane, Maureen ; Hyjek, Elizabath ; Horwitz, Marshall. / Persistent replication of the modified chimeric adenovirus ONYX-015 in both Tumor and stromal cells from a patient with gall bladder carcinoma implants. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 1 I. pp. 33-43.
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abstract = "Purpose: ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicate preferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene, hexon, would demonstrate replication of virus in human tissues. Experimental Design: In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 × 1010 viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication. Results: In situ Reverse transcription -PCR was used to measure expression of hexon. Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins. Conclusions: Evidence for replication of hexon confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.",
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AU - Tan, Jian You

AU - Kaleya, Ron

AU - Rozenblit, Alla

AU - Makower, Della F.

AU - Edelman, Morris

AU - Lane, Maureen

AU - Hyjek, Elizabath

AU - Horwitz, Marshall

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N2 - Purpose: ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicate preferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene, hexon, would demonstrate replication of virus in human tissues. Experimental Design: In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 × 1010 viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication. Results: In situ Reverse transcription -PCR was used to measure expression of hexon. Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins. Conclusions: Evidence for replication of hexon confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.

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