Evidence map›Paper›PMID 24777680›Full record

ArticleCancer immunology research2013

Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity.

Jian Yan, Panyupa Pankhong, Thomas H Shin, Nyamekye Obeng-Adjei, Matthew P Morrow, Jewell N Walters, Amir S Khan, Niranjan Y Sardesai, David B Weiner

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
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  12. Telomeres and Cancer.Life (Basel, Switzerland) · 2021
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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

9 authors at 2 institutions in 1 country.

Jian Yan *Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422.
Panyupa Pankhong *Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Thomas H ShinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nyamekye Obeng-AdjeiDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthew P MorrowInovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422.
Jewell N WaltersDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Amir S KhanInovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422.
Niranjan Y SardesaiInovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422.
David B WeinerDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
University of Pennsylvania · USInovio Pharmaceuticals (United States) · US

Funding

Training In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7M
NCI NIH HHS 5T32CA115299-07NCI NIH HHS T32 CA115299
6 · The paper itself

Abstract

High levels of human telomerase reverse transcriptase (hTERT) are detected in more than 85% of human cancers. Immunologic analysis supports that hTERT is a widely applicable target recognized by T cells and can be potentially studied as a broad cancer immunotherapeutic, or a unique line of defense against tumor recurrence. There remains an urgent need to develop more potent hTERT vaccines. Here, a synthetic highly optimized full-length hTERT DNA vaccine (phTERT) was designed and the induced immunity was examined in mice and non-human primates (NHP). When delivered by electroporation, phTERT elicited strong, broad hTERT-specific CD8 T-cell responses including induction of T cells expressing CD107a, IFN-γ, and TNF-α in mice. The ability of phTERT to overcome tolerance was evaluated in an NHP model, whose TERT is 96% homologous to that of hTERT. Immunized monkeys exhibited robust [average 1,834 spot forming unit (SFU)/10(6) peripheral blood mononuclear cells (PBMC)], diverse (multiple immunodominant epitopes) IFN-γ responses and antigen-specific perforin release (average 332 SFU/10(6) PBMCs), suggesting that phTERT breaks tolerance and induces potent cytotoxic responses in this human-relevant model. Moreover, in an HPV16-associated tumor model, vaccination of phTERT slows tumor growth and improves survival rate in both prophylactic and therapeutic studies. Finally, in vivo cytotoxicity assay confirmed that phTERT-induced CD8 T cells exhibited specific cytotoxic T lymphocyte (CTL) activity, capable of eliminating hTERT-pulsed target cells. These findings support that this synthetic electroporation-delivered DNA phTERT may have a role as a broad therapeutic cancer vaccine candidate.

Indexed as

AnimalsCancer VaccinesCell Line, TumorFemaleHumansImmune ToleranceImmunityMacaca mulattaMiceNeoplasm Recurrence, LocalNeoplasmsTelomeraseT-Lymphocytes, CytotoxicVaccines, DNACancer VaccinesTelomeraseTERT protein, humanVaccines, DNA

Identifiers

PMID24777680
PMCPMC4096936
OpenAlexW1996814108

What OpenQuestion holds

Textmetadata
LicenceTDM
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.