Evidence map›Paper›PMID 25661083›Full record

ArticleGut2016

Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein.

Giuseppe A Sautto, Karin Wisskirchen, Nicola Clementi, Matteo Castelli, Roberta A Diotti, Julia Graf, Massimo Clementi, Roberto Burioni, Ulrike Protzer, Nicasio Mancini

Open access · hybridAbstract readEvaluation Study
In one paragraph

Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
2.7field-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

52 citing papers in PubMed, 96 citations in OpenAlex.

  1. Beyond Oncology: Exploring the Expanding Role of CAR T Cell Therapy in Autoimmune and Infectious Diseases-A Systematic Review.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. In vivo CAR engineering for immunotherapy.Nature reviews. Immunology · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025
    Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Synergistic integration of mRNA-LNP with CAR-engineered immune cells: Pioneering progress in immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  17. Article
  18. Review
  19. Review
  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

10 authors at 2 institutions in 3 countries.

Giuseppe A SauttoLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Karin WisskirchenInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Nicola ClementiLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Matteo CastelliLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Roberta A DiottiLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Julia GrafInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Massimo ClementiLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Roberto BurioniLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Ulrike ProtzerInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Nicasio ManciniLaboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milan, Italy.
Vita-Salute San Raffaele University · ITHelmholtz Zentrum München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2).

designAnti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc).

resultsIn this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes.

conclusionsClearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool.

Indexed as

Antibodies, Monoclonal, HumanizedCell EngineeringCells, CulturedHepacivirusHepatitis CHepatocytesHumansImmunotherapyReceptors, Antigen, T-CellT-LymphocytesViral Envelope ProteinsAntibodies, Monoclonal, Humanizedglycoprotein E2, Hepatitis C virusReceptors, Antigen, T-CellViral Envelope ProteinsHEPATITIS CIMMUNE RESPONSEIMMUNOLOGY IN HEPATOLOGYIMMUNOTHERAPYINFECTIOUS DISEASE

Identifiers

PMID25661083
PMCPMC4789830
OpenAlexW2144659726

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.