Evidence map›Paper›PMID 32819976›Full record

ArticleJournal for immunotherapy of cancer2020

Chimeric Ad5.F35 vector evades anti-adenovirus serotype 5 neutralization opposing GUCY2C-targeted antitumor immunity.

John C Flickinger, Jagmohan Singh, Robert Carlson, Elinor Leong, Trevor R Baybutt, Joshua Barton, Ellen Caparosa, Amanda Pattison, Jeffrey A Rappaport, Jamin Roh and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% of its field
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. The seroprevalence of adenoviruses since 2000Emerging microbes & infections · 2025
    Review
  7. Review
  8. Virus Against Cancer: Paradigm-Shifting Biological Concepts.Current neurology and neuroscience reports · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
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

14 authors at 1 institution in 1 country.

John C Flickinger *Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jagmohan Singh *Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Robert CarlsonDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Elinor LeongDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Trevor R BaybuttDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Joshua BartonDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Ellen CaparosaDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Amanda PattisonDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jeffrey A RappaportDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jamin RohDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Tingting ZhanDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Babar BashirDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Scott A WaldmanDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Adam E SnookDepartment of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA adam.snook@jefferson.edu.ORCID 0000-0001-9216-4560
Thomas Jefferson University · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Andrew Chapman · 1995 to 2026
$94.8M
CLINICAL PHARMACOLOGY TRAINING PROGRAMT32GM008562 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI WALTER K KRAFT, Scott A. Waldman · 1995 to 2026
$10.2M
Guanylin GUCY2C axis in Colorectal Cancer InitiationR01CA204481 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2017 to 2021
$1.8M
(PQ1) GUCY2C hormone loss translates APC-Beta-catenin mutations into epithelial transformationR01CA206026 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2016 to 2020
$1.8M
Restoring Guanylin-Guanylate cyclase C Signaling to Prevent Colorectal CancerF30CA232469 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RAPPAPORT, JEFFREY · 2018 to 2022
$188k
Silencing the uroguanylin-GUCY2C gut-brain axis mediates leptin resistance in obesityF30DK127639 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI BARTON, JOSHUA R · 2020 to 2024
$175k
Reactivating the GUCY2C signaling axis opposes oncogenic B-catenin for cancer chemopreventionF31CA225123 · NCI · THOMAS JEFFERSON UNIVERSITY · PI PATTISON, AMANDA · 2018 to 2020
$112k
NCI NIH HHS F30 CA232469NCI NIH HHS F31 CA225123NCI NIH HHS P30 CA056036NCI NIH HHS R01 CA204481NCI NIH HHS R01 CA206026NIDDK NIH HHS F30 DK127639NIGMS NIH HHS T32 GM008562
6 · The paper itself

Abstract

backgroundAdenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines. Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.

methodsHere, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) derived from the capsid of Ad5 and fiber of the rare adenovirus serotype 35 (Ad35) to induce immune responses to the tumor-associated antigen guanylyl cyclase C (GUCY2C).

resultsIn the absence of pre-existing immunity to Ad5, GUCY2C-specific T-cell responses and antitumor efficacy induced by Ad5.F35 were comparable to Ad5 in a mouse model of metastatic colorectal cancer. Furthermore, like Ad5, Ad5.F35 vector expressing GUCY2C was safe and produced no toxicity in tissues with, or without, GUCY2C expression. Importantly, this chimeric vector resisted neutralization in Ad5-immunized mice and by sera collected from patients with colorectal cancer naturally exposed to Ad5.

conclusionsThese data suggest that Ad5.F35-based vaccines targeting GUCY2C, or other tumor or pathogen antigens, may produce clinically relevant immune responses in more (≥90%) patients compared with Ad5-based vaccines (~50%).

Indexed as

AnimalsChimerismDisease Models, AnimalFemaleHumansImmunotherapyMaleMiceReceptors, EnterotoxinGUCY2C protein, humanReceptors, Enterotoxinactivegastrointestinal neoplasmsimmunizationimmunogenicityimmunotherapyvaccinationvaccine

Identifiers

PMID32819976
PMCPMC7443303
OpenAlexW3067763113

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.