Evidence map›Paper›PMID 38327807›Full record

ArticleMolecular therapy. Methods & clinical development2024

Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

Elizabeth Ogando-Rivas, Paul Castillo, Changlin Yang, Vrunda Trivedi, Dingpeng Zhang, Fernanda Pohl-Guimarães, Ruixuan Liu, Arnav Barpujari, Kate M Candelario, Hector Mendez-Gomez and 2 more

Abstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Elizabeth Ogando-RivasUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Paul CastilloUF Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Changlin YangUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Vrunda TrivediUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Dingpeng ZhangUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Fernanda Pohl-GuimarãesUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Ruixuan LiuUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Arnav BarpujariUF Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Kate M CandelarioUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Hector Mendez-GomezUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Elias J SayourUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Duane A MitchellUF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRβ repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions.

Indexed as

adoptive T cellsantigen-presenting cellshypomutated regionsRNA-based immunotherapySARS-CoV-2

Identifiers

PMID38327807
PMCPMC10847775

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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.