# Intratumoral generation of F-Ade to ablate low growth fraction HNSCC

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $442,836

## Abstract

This study will address a novel tumor cell killing approach designed to ablate solid tumors with a low
proliferative index and the attendant neoplastic progenitor cells. Our laboratory has pursued 2-Fluoroadenine
(F-Ade), a purine base that disrupts DNA, RNA, and protein synthesis, as an anticancer compound. Here, we
utilize F-araAMP, a clinically approved drug that otherwise has negligible activity against solid tumors, as an F-
Ade precursor. F-Ade is generated from fludarabine by intratumoral expression of the E. coli purine nucleoside
phosphorylase (PNP) gene. The strategy has demonstrated significant efficacy in comprehensive nonclinical
studies and a recently completed, first-in-human trial of head and neck squamous cell carcinoma (HNSCC).
The scientific objectives of the current proposal are to establish strong and safe tumor regressions based on
activity across multiple HNSCC tumor types in vitro and in vivo, and to augment delivery and safety of the PNP
gene (Specific Aims 1 and 2). The experiments will evaluate mechanism of action (nucleoside cleavage, PNP
transgene activity, disruption of the noncycling tumor cell compartment) (Specific Aim 3). Our experimental
plan is multidisciplinary (biomedical engineering, nanoparticle chemistry, DNA/RNA delivery technology,
nucleoside metabolism and enzymology), mutually reinforcing, and directed by a senior investigator trained in
oncology (Sorscher) and a biomedical engineering scientist beginning his research career (Dahlman).
Translational potential is high, as indicated by a successful Phase 1 trial of the technology, formal orphan drug
designation, and a Phase 2 study approved by FDA.

## Key facts

- **NIH application ID:** 9959187
- **Project number:** 5R01DE026941-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Eric J SORSCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,836
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959187

## Citation

> US National Institutes of Health, RePORTER application 9959187, Intratumoral generation of F-Ade to ablate low growth fraction HNSCC (5R01DE026941-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9959187. Licensed CC0.

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