Evidence map›Paper›PMID 30024272›Full record

ArticleHuman gene therapy2019

Purification of mRNA Encoding Chimeric Antigen Receptor Is Critical for Generation of a Robust T-Cell Response.

Jessica B Foster, Namrata Choudhari, Jessica Perazzelli, Julie Storm, Ted J Hofmann, Payal Jain, Phillip B Storm, Norbert Pardi, Drew Weissman, Angela J Waanders and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Human gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
3.8field-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

83 citing papers in PubMed, 129 citations in OpenAlex.

  1. Trial
  2. Advances inMolecular therapy. Nucleic acids · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. CAR-T therapy: Advances in respiratory diseases.Chinese medical journal pulmonary and critical care medicine · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases.Molecular therapy. Methods & clinical development · 2025
    Review
  17. Article
  18. Article
  19. Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  20. Article

23 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Jessica B Foster1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Namrata Choudhari3 Division of Neurosurgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Jessica Perazzelli1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Julie Storm1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Ted J Hofmann1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Payal Jain3 Division of Neurosurgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Phillip B Storm2 Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Norbert Pardi6 Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Drew Weissman6 Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Angela J Waanders1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Stephan A Grupp1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Katalin Karikó7 BioNTech RNA Pharmaceuticals, Mainz, Germany.
Adam C Resnick2 Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
David M Barrett1 Division of Oncology,, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USBioNTech (Germany) · DE

Funding

Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARL H. JUNE · 2017 to 2026
$26.8M
CANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4M
Nucleoside modified mRNA based HIV vaccineR01AI124429 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISSMAN, DREW · 2016 to 2019
$3.4M
NCI NIH HHS P01 CA214278NCI NIH HHS T32 CA009615NIAID NIH HHS R01 AI124429
6 · The paper itself

Abstract

T cells made with messenger RNA (mRNA) encoding chimeric antigen receptor (CAR) offer a safe alternative to those transduced with viral CARs by mitigating the side effects of constitutively active T cells. Previous studies have shown that mRNA CAR T cells are transiently effective but lack persistence and potency across tumor types. It was hypothesized that the efficacy of mRNA CARs could be improved by utilizing recent advancements in RNA technology, such as incorporating a modified nucleoside, 1-methylpseudouridine, into the mRNA and applying a novel purification method using RNase III to eliminate dsRNA contaminants. T cells electroporated with nucleoside-modified and purified mRNA encoding CD19 CAR showed an initial twofold increase in CAR surface expression, as well as a twofold improvement in cytotoxic killing of leukemia cells that persisted up to 5 days. T cells generated with nucleoside-modified and purified CAR mRNA also showed reduced expression of checkpoint regulators and a differential pattern of genetic activation compared to those made with conventional mRNA. In vivo studies using a leukemia mouse model revealed that the most robust 100-fold suppression of leukemic burden was achieved using T cells electroporated with purified mRNAs, regardless of their nucleoside modification. The results provide a novel approach to generate mRNA for clinical trials, and poise mRNA CAR T cells for increased efficacy during testing as new CAR targets emerge.

Indexed as

Adoptive TransferElectroporationLeukemiaReceptors, Chimeric AntigenRNA, MessengerAnimalsAntigens, CD19Cell Line, TumorHumansMiceMice, Inbred NODMice, KnockoutMice, SCIDT-LymphocytesXenograft Model Antitumor AssaysAntigens, CD19CD19 molecule, humanReceptors, Chimeric AntigenRNA, Messengerchimeric antigen receptorimmunotherapyRNAT cell

Identifiers

PMID30024272
PMCPMC6383579
OpenAlexW2884096061

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.