Evidence map›Paper›PMID 25965393›Full record

ArticleGene therapy2015

Lentivirus-induced 'Smart' dendritic cells: Pharmacodynamics and GMP-compliant production for immunotherapy against TRP2-positive melanoma.

B S Sundarasetty, L Chan, D Darling, G Giunti, F Farzaneh, F Schenck, S Naundorf, K Kuehlcke, E Ruggiero, M Schmidt and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2015. 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
2.2field-weighted citation impact, top 12% 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, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Therapeutic cancer vaccines.Nature reviews. Cancer · 2021
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  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

19 authors at 4 institutions in 3 countries.

B S SundarasettyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
L ChanDepartment of Hematological Medicine, Cell and Gene Therapy at King's, The Rayne Institute, King's College London, London, UK.
D DarlingDepartment of Hematological Medicine, Cell and Gene Therapy at King's, The Rayne Institute, King's College London, London, UK.
G GiuntiDepartment of Hematological Medicine, Cell and Gene Therapy at King's, The Rayne Institute, King's College London, London, UK.
F FarzanehDepartment of Hematological Medicine, Cell and Gene Therapy at King's, The Rayne Institute, King's College London, London, UK.
F SchenckDepartment of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
S NaundorfEUFETS GmbH, Idar-Oberstein, Heidelberg, Germany.
K KuehlckeEUFETS GmbH, Idar-Oberstein, Heidelberg, Germany.
E RuggieroDivision of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
M SchmidtDivision of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
C von KalleDivision of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
M RotheDepartment of Experimental Hematology, Hannover, Germany.
D S B HoonJohn Wayne Cancer Institute, Santa Monica, CA, USA.
L GeraschDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
C FigueiredoDepartment of Transfusion Medicine, Hannover Medical School, Hannover, Germany.
U KoehlInstitute for Cell Therapeutics and GMP core facility IFB-Tx, Hannover Medical School, Hannover, Germany.
R BlasczykDepartment of Transfusion Medicine, Hannover Medical School, Hannover, Germany.
R GutzmerDepartment of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
R StripeckeDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Medizinische Hochschule Hannover · DEKing's College London · GBNational Center for Tumor Diseases · DESaint John's Health Center · US

Funding

Biotechnology and Biological Sciences Research Council BB/E005896/1
6 · The paper itself

Abstract

Monocyte-derived conventional dendritic cells (ConvDCs) loaded with melanoma antigens showed modest responses in clinical trials. Efficacy studies were hampered by difficulties in ConvDC manufacturing and low potency. Overcoming these issues, we demonstrated higher potency of lentiviral vector (LV)-programmed DCs. Monocytes were directly induced to self-differentiate into DCs (SmartDC-TRP2) upon transduction with a tricistronic LV encoding for cytokines (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4)) and a melanoma antigen (tyrosinase-related protein 2 (TRP2)). Here, SmartDC-TRP2 generated with monocytes from five advanced melanoma patients were tested in autologous DC:T cell stimulation assays, validating the activation of functional TRP2-specific cytotoxic T lymphocytes (CTLs) for all patients. We described methods compliant to good manufacturing practices (GMP) to produce LV and SmartDC-TRP2. Feasibility of monocyte transduction in a bag system and cryopreservation following a 24-h standard operating procedure were achieved. After thawing, 50% of the initial monocyte input was recovered and SmartDC-TRP2 self-differentiated in vitro, showing uniform expression of DC markers, detectable LV copies and a polyclonal LV integration pattern not biased to oncogenic loci. GMP-grade SmartDC-TRP2 expanded TRP2-specific autologous CTLs in vitro. These results demonstrated a simpler GMP-compliant method of manufacturing an effective individualized DC vaccine. Such DC vaccine, when in combination with checkpoint inhibition therapies, might provide higher specificity against melanoma.

Indexed as

Cancer VaccinesDendritic CellsGenetic VectorsHEK293 CellsHumansImmunotherapyLentivirusMelanomaMembrane ProteinsPeptide FragmentsT-Lymphocytes, CytotoxicCancer VaccinesMembrane ProteinsPeptide Fragmentspeptide SVYDFFVWL

Identifiers

PMID25965393
PMCPMC4561294
OpenAlexW2125000186

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.