Intratumoral generation of 2-fluoroadenine to treat solid malignancies of the head and neck

• Type of Material: Article
• Authors: Turang E. Behbahani, Emory University; Eben L. Rosenthal, Stanford University; William B. Parker, PNP Therapeutics Inc.; Eric Sorscher, Emory University
• Language: English
• Date: 2019-06-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 John Wiley & Sons, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1002/hed.25627
• Title of Journal or Parent Work: Head & Neck: Journal of the Sciences and Specialities of the Head and Neck
• Volume: 41
• Issue: 6
• Start Page: 1979
• End Page: 1983
• Grant/Funding Information: This work was funded through grant awards from National Institute of Health (Ruth L. Kirschstein Institutional National Research Service Award 5T32CA160040 and National Institute of Dental and Craniofacial Research, NIDCR, RO1DE026941) and the Georgia Research Alliance (GRA.VL19.C3).
• Keywords: Expression; Adenovirus; Science & Technology; Life Sciences & Biomedicine; Prodrug; Purine nucleoside psosphorylase; Gene therapy; Delivery; gene transfer; Fludarabine phosphate; 2-fluoroadenine; Prostate cancer; Surgery; Otorhinolaryngology; purine nucleoside phosphorylase; Tumors; HNSCC; Measles virus; clinical trial
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

This report describes treatment of locoregional head and neck squamous cell carcinoma (HNSCC) by an innovative, experimental strategy involving generation of a robust anti-cancer agent (2-fluoroadenine [F-Ade]) following transduction by Escherichia coli purine nucleoside phosphorylase (PNP) in a small number of tumor cells. F-Ade works by a unique mechanism of action (ablation of RNA and protein synthesis) and confers tumor regressions of otherwise refractory HNSCC in human subjects. Clinical studies have now advanced to a pivotal (registration-directed) trial involving locoregional HNSCC, with plans to begin subject enrollment late in 2018. The present review is the first to summarize use of PNP in the context of HNSCC, and provides background regarding this emerging anti-cancer approach.