Open AccessEvaluating antitumor activity of Escherichia coli purine nucleoside phosphorylase against head and neck patient‐derived xenografts
Author(s) -
Rab Regina,
Ehrhardt Annette,
Achyut Bhagelu R.,
Joshi Disha,
GilbertRoss Melissa,
Huang Chunzi,
Floyd Katharine,
Borovjagin Anton V.,
Parker William B.,
Sorscher Eric J.,
Hong Jeong S.
Publication year - 2023
Publication title -
cancer reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.261
H-Index - 5
ISSN - 2573-8348
DOI - 10.1002/cnr2.1708
Subject(s) - purine nucleoside phosphorylase , purine , cancer research , prodrug , nucleoside analogue , fludarabine , cytotoxicity , nucleoside , head and neck cancer , chemistry , biology , cancer , enzyme , medicine , biochemistry , chemotherapy , in vitro , cyclophosphamide
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.