Evidence map›Paper›PMID 30996140›Full record

ArticleJCI insight2019

DNA-encoded bispecific T cell engagers and antibodies present long-term antitumor activity.

Alfredo Perales-Puchalt, Elizabeth K Duperret, Xue Yang, Patricia Hernandez, Krzysztof Wojtak, Xizhou Zhu, Seang-Hwan Jung, Edgar Tello-Ruiz, Megan C Wise, Luis J Montaner and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. DNA-based immunotherapy for cancer: In vivo approaches for recalcitrant targets.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. MultivalentMolecular therapy oncolytics · 2023
    Article
  13. Article
  14. Review
  15. Molecular therapy oncolytics · 2022
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
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 at 2 institutions in 1 country.

Alfredo Perales-PuchaltVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Elizabeth K DuperretVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Xue YangVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Patricia HernandezVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Krzysztof WojtakVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Xizhou ZhuVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Seang-Hwan JungVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Edgar Tello-RuizVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Megan C WiseInovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
Luis J MontanerVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Kar MuthumaniVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
David B WeinerVaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA.
The Wistar Institute · USInovio Pharmaceuticals (United States) · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Targeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1M
Targeting hyaluronan in the tumor microenvironment to improve DNA vaccine immunotherapyF32CA213795 · NCI · WISTAR INSTITUTE · PI DUPERRET, ELIZABETH KENNEDY · 2017 to 2018
$94k
NCI NIH HHS F32 CA213795NCI NIH HHS P30 CA010815NCI NIH HHS P50 CA174523NCI NIH HHS T32 CA009171
6 · The paper itself

Abstract

Specific antibody therapy, including mAbs and bispecific T cell engagers (BiTEs), are important new tools for cancer immunotherapy. However, these approaches are slow to develop and may be limited in their production, thus restricting the patients who can access these treatments. BiTEs exhibit a particularly short half-life and difficult production. The development of an approach allowing simplified development, delivery, and in vivo production would be an important advance. Here we describe the development of a designed synthetic DNA plasmid, which we optimized to permit high expression of an anti-HER2 antibody (HER2dMAb) and delivered it into animals through adaptive electroporation. HER2dMAb was efficiently expressed in vitro and in vivo, reaching levels of 50 μg/ml in mouse sera. Mechanistically, HER2dMAb blocked HER2 signaling and induced antibody-dependent cytotoxicity. HER2dMAb delayed tumor progression for HER2-expressing ovarian and breast cancer models. We next used the HER2dMAb single-chain variable fragment portion to engineer a DNA-encoded BiTE (DBiTE). This HER2DBiTE was expressed in vivo for approximately 4 months after a single administration. The HER2DBiTE was highly cytolytic and delayed cancer progression in mice. These studies illustrate an approach to generate DBiTEs in vivo, which represent promising immunotherapies for HER2+ tumors, including ovarian and potentially other cancers.

Indexed as

AnimalsAntibodies, BispecificAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCell Line, TumorDrug Delivery SystemsElectroporationErb-b2 Receptor Tyrosine KinasesFemaleHumansMaleMiceNeoplasmsPlasmidsT-LymphocytesXenograft Model Antitumor AssaysAntibodies, BispecificAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesCancer gene therapyCancer immunotherapyImmunologyOncology

Identifiers

PMID30996140
PMCPMC6538381
OpenAlexW2937887082

What OpenQuestion holds

Textmetadata
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.