Evidence map›Paper›PMID 42171604›Full record

ArticleJCI insight2026

Broadening activity of checkpoint blockade agents by intratumoral nucleoside cleavage.

Regina Rab, Jeong S Hong, Brendan Lc Kinney, Nicole C Schmitt, William B Parker, Adrianna Westbrook, Kelsey B Bennion, Mandy L Ford, Douglas H Weitzel, Paula L Miliani de Marval and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Regina RabDivision of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Jeong S HongDivision of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Brendan Lc KinneyDepartment of Otolaryngology - Head and Neck Surgery, and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
Nicole C SchmittDepartment of Otolaryngology - Head and Neck Surgery, and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
William B ParkerPNP Therapeutics Inc., Birmingham, Alabama, USA.
Adrianna WestbrookPediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Kelsey B BennionDepartment of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Mandy L FordDepartment of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Douglas H WeitzelCharles River Laboratories and.
Paula L Miliani de MarvalSpringWorks Therapeutics, Research Triangle Park, North Carolina, USA.
Eric J SorscherDivision of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Annette EhrhardtDivision of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.

Funding

Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Intratumoral generation of F-Ade to ablate low growth fraction HNSCCR01DE026941 · NIDCR · EMORY UNIVERSITY · PI SORSCHER, ERIC J · 2017 to 2021
$2.3M
NCI NIH HHS P30 CA138292NIDCR NIH HHS R01 DE026941
6 · The paper itself

Abstract

We investigated whether destroying malignant cells and the associated tumor microenvironment (TME) by focal gene therapy would broaden immune checkpoint inhibitor (ICI) effectiveness. We show that ICI antitumor activity against syngeneic (murine) triple-negative breast cancer (TNBC) was augmented when a therapeutic transgene (purine nucleoside phosphorylase, referred to here as E. coli PNP) was used to cleave fludarabine (2-fluoro-arabinofuranosyl adenine) to the anticancer purine base, 2-fluoroadenine (F-Ade). We also established strong repression of anatomically distant, non-PNP-expressing tumors being treated by the same strategy. TNBC cytoreduction was associated with decreased intratumoral PD1+ Tregs, increased granzyme B+ NK cells, elevated MKI67+ T8 cells, and rapid immune clearance. Because F-Ade works by a mechanism that destroys quiescent neoplastic and supporting cells in the microenvironment, and since resistance to ICIs depends upon an intact TME, tumor killing by this approach offers a means to sensitize refractory malignancies to immune ablation and points to broad applicability against numerous cancer subtypes.

Indexed as

Genetic TherapyImmune Checkpoint InhibitorsPurine-Nucleoside PhosphorylaseTriple Negative Breast NeoplasmsVidarabineAdenineAnimalsCell Line, TumorFemaleGene Therapy AgentsHumansKiller Cells, NaturalMiceNucleosidesProgrammed Cell Death 1 ReceptorTumor MicroenvironmentAdeninefludarabineImmune Checkpoint InhibitorsNucleosidesProgrammed Cell Death 1 ReceptorPurine-Nucleoside PhosphorylaseVidarabineBreast cancerCancer gene therapyCancer immunotherapyGeneticsOncology

Identifiers

PMID42171604
PMCPMC13232721

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.