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Author Notes:

Eric J. Sorscher, Emory University School of Medicine, 1760 Haygood Drive, Suite 280, Atlanta, GA, 30322, USA. Email: esorscher@emory.edu

Regina Rab: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); validation (equal); visualization (equal); writing – review and editing (equal). Annette Ehrhardt: Conceptualization (equal); data curation (equal); investigation (equal); methodology (equal); supervision (equal); visualization (equal); writing – review and editing (equal). Bhagelu R. Achyut: Data curation (equal); formal analysis (equal); investigation (equal); visualization (equal); writing – review and editing (equal). Disha Joshi: Data curation (equal); investigation (equal); methodology (equal); validation (equal); writing – review and editing (equal). Melissa Gilbert‐Ross: Funding acquisition (equal); methodology (equal); project administration (equal); resources (equal); supervision (equal); writing – review and editing (equal). Chunzi Huang: Data curation (equal); investigation (equal); methodology (equal). Katharine Floyd: Data curation (equal); investigation (equal); methodology (equal). Anton V. Borovjagin: Funding acquisition (equal); investigation (equal); methodology (equal); resources (equal); writing – review and editing (equal). William B. Parker: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); supervision (equal); writing – review and editing (equal). Eric J. Sorscher: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Jeong S. Hong: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); supervision (equal); validation (equal); visualization (equal); writing – review and editing (equal).

Research was supported in part by the Cancer Animal Models shared resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. Funding was also provided by NIH grant R01DE026941. We wish to thank the NCI Patient‐Derived Models Repository (PDMR), NCI‐Frederick, Frederick National Laboratory for Cancer Research, Frederick, MD https://pdmr.cancer.gov/ for providing PDX cells. We would also like to acknowledge Dr. Ilya Ulasov (The Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, World‐Class Research Center “Digital biodesign and personalized healthcare”, Sechenov First Moscow State Medical University, Moscow, Russia and Department of Neurological Surgery, Northwestern University, Chicago, USA) for technical assistance with propagation and purification of Ad vectors.

Parker and Sorscher have ownership interests in PNP Therapeutics and serve on the Board of Directors for the company, which develops products used in research described by the paper. Parker and Sorscher are also inventors of technology being evaluated in studies described by this report. The terms of this arrangement for Sorscher have been reviewed and approved by Emory University in accordance with its conflict‐of‐interest policies. Jeong Hong also has minor equity interest in this company. Other authors have no conflict‐of‐interest to report.

Subjects:

Keywords:

  • gene transfer
  • head and neck squamous cell carcinoma
  • patient-derived xenografts
  • purine nucleoside phosphorylase
  • tropism modified adenovirus
  • Humans
  • Purine-Nucleoside Phosphorylase
  • Escherichia coli
  • Heterografts
  • Genetic Vectors
  • Genetic Therapy
  • Head and Neck Neoplasms
  • Adenoviridae

Evaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient-derived xenografts

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Journal Title:

Cancer Reports

Volume:

Volume 6, Number 2

Publisher:

, Pages e1708-e1708

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.

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