Evidence map›Paper›PMID 15496964›Full record

ArticleGene therapy2004

Combining high selectivity of replication with fiber chimerism for effective adenoviral oncolysis of CAR-negative melanoma cells.

A A Rivera, J Davydova, S Schierer, M Wang, V Krasnykh, M Yamamoto, D T Curiel, D M Nettelbeck

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.4field-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

31 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Concepts in Oncolytic Adenovirus Therapy.International journal of molecular sciences · 2021
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Conditionally replicating adenovirus expressing TIMP2 for ovarian cancer therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011
    Article
  17. Article
  18. Article
  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

8 authors at 1 institution in 1 country.

A A RiveraDivision of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
J Davydova
S Schierer
M Wang
V Krasnykh
M Yamamoto
D T Curiel
D M Nettelbeck
University of Alabama at Birmingham · US

Funding

Enhanced CRAd for Pancreatic CancerR01CA094084 · NCI · UNIVERSITY OF MINNESOTA · PI YAMAMOTO, MASATO · 2002 to 2013
$2.7M
REPLICATIVE ADENOVIRUSES WITH ENHANCED INFECTIVITYR01CA083821 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CURIEL, DAVID TERRY · 2000 to 2008
$1.9M
Canine model for evaluating CRAD efficacyR01CA093796 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SIEGAL, GENE P · 2002 to 2005
$1.1M
NCI NIH HHS R01 CA83591NCI NIH HHS R01 CA83821NCI NIH HHS R01 CA93796NCI NIH HHS R01 CA94084
6 · The paper itself

Abstract

Oncolytic adenoviruses constitute a new and promising tool for cancer treatment that has been rapidly translated into clinical trials. However, minimal or absent expression of the adenovirus serotype 5 (Ad5) receptor CAR (coxsackievirus and adenovirus receptor) on cancer cells represents a major limitation for Ad5-based oncolysis. Here, we report on the resistance of CAR-negative primary melanoma cells to cell killing by wild-type Ad5 (Ad5wt) even after high titer infection, thus underlining the need for tropism-modification of oncolytic adenoviruses. We engineered a new generation of oncolytic adenoviruses that exhibit both efficient target cell infection by swapping Ad5 fiber domains with those of Ad serotype 3, which binds to a receptor distinct from CAR, and targeted virus replication. Fiber chimerism resulted in efficient cytopathicity to primary melanoma cells, which was at least 10(4)-fold increased relative to Ad5wt. Since viral infectivity mediated by such modified viral capsids was not cell type-specific, it was pivotal to carefully restrict adenoviral replication to target cells. Towards this end, we replaced both E1A and E4 promoters of fiber chimeric viruses by tyrosinase enhancer/promoter constructs. The resulting viruses showed melanoma-specific expression of E1A and E4 and combined efficient virus replication and cell killing in melanoma cell lines and primary melanoma cells with a remarkable specificity profile that implements strong attenuation in nonmelanoma cells, including normal fibroblasts and keratinocytes.

Indexed as

AdenoviridaeAdenovirus E1A ProteinsAdenovirus E4 ProteinsCapsid ProteinsCell DeathChimerismCoxsackie and Adenovirus Receptor-Like Membrane ProteinCytopathogenic Effect, ViralHumansMelanomaMembrane ProteinsNeoplasm ProteinsPlasmidsPromoter Regions, GeneticReceptors, VirusTropismAdenovirus E1A ProteinsAdenovirus E4 ProteinsCapsid ProteinsCLMP protein, humanCoxsackie and Adenovirus Receptor-Like Membrane Proteinhexon capsid protein, AdenovirusMembrane ProteinsNeoplasm ProteinsReceptors, Virus

Identifiers

PMID15496964
OpenAlexW2081190165

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.