Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts
Abstract Background Purine nucleoside phosphorylase (PNP) gene transfer represents a promising approach to treatment of head and neck malignancies. We tested recombinant adenovirus already in phase I/II clinical testing and leading‐edge patient‐derived xenografts (PDX) as a means to optimize this th...
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1708 |
| _version_ | 1797902692909056000 |
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| author | Regina Rab Annette Ehrhardt Bhagelu R. Achyut Disha Joshi Melissa Gilbert‐Ross Chunzi Huang Katharine Floyd Anton V. Borovjagin William B. Parker Eric J. Sorscher Jeong S. Hong |
| author_facet | Regina Rab Annette Ehrhardt Bhagelu R. Achyut Disha Joshi Melissa Gilbert‐Ross Chunzi Huang Katharine Floyd Anton V. Borovjagin William B. Parker Eric J. Sorscher Jeong S. Hong |
| author_sort | Regina Rab |
| collection | DOAJ |
| description | Abstract Background Purine nucleoside phosphorylase (PNP) gene transfer represents a promising approach to treatment of head and neck malignancies. We tested recombinant adenovirus already in phase I/II clinical testing and leading‐edge patient‐derived xenografts (PDX) as a means to optimize this therapeutic strategy. Methods Our experiments investigated purine base cytotoxicity, PNP enzyme activity following treatment of malignant tissue, tumor mass regression, viral receptor studies, and transduction by tropism‐modified adenovirus. Results Replication deficient vector efficiently transduced PDX cells and mediated significant anticancer effect following treatment with fludarabine phosphate in vivo. Either 6‐methylpurine or 2‐fluoroadenine (toxic molecules generated by the PNP approach) ablated head and neck cancer cell proliferation. High levels of adenovirus‐3 specific receptors were detected in human tumor models, and vector was evaluated that utilizes this pathway. Conclusions Our studies provide the scientific foundation necessary to improve PNP prodrug cleavage and advance a new treatment for head and neck cancer. |
| first_indexed | 2024-04-10T09:21:40Z |
| format | Article |
| id | doaj.art-15b3156b4be14e158f73b9c68fc1972b |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-04-10T09:21:40Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-15b3156b4be14e158f73b9c68fc1972b2023-02-20T10:23:21ZengWileyCancer Reports2573-83482023-02-0162n/an/a10.1002/cnr2.1708Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenograftsRegina Rab0Annette Ehrhardt1Bhagelu R. Achyut2Disha Joshi3Melissa Gilbert‐Ross4Chunzi Huang5Katharine Floyd6Anton V. Borovjagin7William B. Parker8Eric J. Sorscher9Jeong S. Hong10Department of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine Atlanta Georgia USADepartment of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine Atlanta Georgia USAWinship Cancer Institute Emory University School of Medicine Atlanta Georgia USADepartment of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine Atlanta Georgia USAWinship Cancer Institute Emory University School of Medicine Atlanta Georgia USAWinship Cancer Institute Emory University School of Medicine Atlanta Georgia USAWinship Cancer Institute Emory University School of Medicine Atlanta Georgia USADepartment of Biomedical Engineering University of Alabama at Birmingham Birmingham Alabama USADepartment of Pharmacology University of Alabama at Birmingham; PNP Therapeutics, Inc. Birmingham Alabama USADepartment of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine Atlanta Georgia USADepartment of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine Atlanta Georgia USAAbstract Background Purine nucleoside phosphorylase (PNP) gene transfer represents a promising approach to treatment of head and neck malignancies. We tested recombinant adenovirus already in phase I/II clinical testing and leading‐edge patient‐derived xenografts (PDX) as a means to optimize this therapeutic strategy. Methods Our experiments investigated purine base cytotoxicity, PNP enzyme activity following treatment of malignant tissue, tumor mass regression, viral receptor studies, and transduction by tropism‐modified adenovirus. Results Replication deficient vector efficiently transduced PDX cells and mediated significant anticancer effect following treatment with fludarabine phosphate in vivo. Either 6‐methylpurine or 2‐fluoroadenine (toxic molecules generated by the PNP approach) ablated head and neck cancer cell proliferation. High levels of adenovirus‐3 specific receptors were detected in human tumor models, and vector was evaluated that utilizes this pathway. Conclusions Our studies provide the scientific foundation necessary to improve PNP prodrug cleavage and advance a new treatment for head and neck cancer.https://doi.org/10.1002/cnr2.1708gene transferhead and neck squamous cell carcinomapatient‐derived xenograftspurine nucleoside phosphorylasetropism modified adenovirus |
| spellingShingle | Regina Rab Annette Ehrhardt Bhagelu R. Achyut Disha Joshi Melissa Gilbert‐Ross Chunzi Huang Katharine Floyd Anton V. Borovjagin William B. Parker Eric J. Sorscher Jeong S. Hong Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts Cancer Reports gene transfer head and neck squamous cell carcinoma patient‐derived xenografts purine nucleoside phosphorylase tropism modified adenovirus |
| title | Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts |
| title_full | Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts |
| title_fullStr | Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts |
| title_full_unstemmed | Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts |
| title_short | Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts |
| title_sort | evaluating antitumor activity of escherichia coli purine nucleoside phosphorylase against head and neck patient derived xenografts |
| topic | gene transfer head and neck squamous cell carcinoma patient‐derived xenografts purine nucleoside phosphorylase tropism modified adenovirus |
| url | https://doi.org/10.1002/cnr2.1708 |
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